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EPIDEMIC  RESPIRATORY  DISEASE 


EPIDEMIC  RESPIRATORY  DISEASE 

The  Pneumonias  and  Other  Infections  of  the 

Respiratory  Tract  Accompanying 

Influenza  and  Measles 


BY 
EUGENE  L.  OPIE,  M.D. 

COLONEL,  M.  R.  C,  U.  S.  ARMY;   PROFESSOR  OF  PATHOLOGY, 
WASHINGTON  UNIVERSITY   SCHOOL   OF   MEDICINE 

FRANCIS  G.  BLAKE,  M.D. 

MAJOR,   M.  R.   C,   U.   S.  ARMY;    ASSOCIATE  MEMBER  OF  THE 
ROCKEFELLER  INSTITUTE  FOR  MEDICAL  RESEARCH 

JAMES  C.  SMALL,  M.D. 

FORMERLY  FIRST  LIEUTENANT,    M.    C,    U.    S.   ARMY;    BACTERIOLOGIST, 
PHILADELPHIA   GENERAL    HOSPITAL 

THOMAS  M.  RIVERS,  M.D. 

FORMERLY   FIRST   LIEUTENANT,   M.    C,    U.    S.    ARMY;    ASSOCIATE 
IN    BACTERIOLOGY,    JOHNS    HOPKINS    UNIVERSITY 


ILLUSTRATED 


ST.  LOUIS 
C.  V.  MOSBY  COMPANY 

1921 


Copyright,  1921,  By  C.  V.  Mosby  Company 


Press  of 

C.    V.  Mosby  Company 

St.  Louis,   U.  S.  A. 


INTRODUCTION 

Death  from  lobar  pneumonia,  bronchopneumonia  and 
measles,  fatal  with  few  exceptions  in  consequence  of  com- 
plicating pneumonia,  constituted  in  1916  approximately  one- 
sixth  (16.8  per  cent)  of  the  mortality  in  the  army,'  whereas 
in  j 917  the  same  diseases  were  responsible  for  nearly  two- 
thirds  (61.7  per  cent)  of  all  deaths.  During  the  first  half 
of  1918  the  incidence  of  pneumonia  steadily  increased  and 
in  some  army  camps  there  were  extensive  outbreaks  of  un- 
usually severe  pneumonia. 

In  July,  1918,  the  Surgeon  General  assigned  a  group  of 
medical  officers  to  the  study  of  the  pneumonias  prevalent 
in  the  army  and  stationed  them  at  Camp  Funston,  Kansas. 
At  the  base  hospital  of  this  camp  all  cases  of  pneumonia  oc- 
curring among  troops  assembled  in  the  camp  were  studied, 
but  during  the  month  of  August  there  were  few  cases  of 
pneumonia  and  these  were  of  mild  type. 

Pneumonia  which  occurred  at  Camp  Funston  during  Au- 
gust was  almost  wholly  limited  to  recently  recruited  colored 
troops  from  southern  states  (Louisiana,  Mississippi). 
There  was  a  low  rate  of  mortality,  and  few  complication?. 
This  pneumonia  exhibited  a  noteworthy  difference  in  etiol- 
ogy from  that  usually  seen  in  civil  life,  for  it  was' associated 
with  a  high  incidence  of  those  types  of  pneumococci  which 
occur  in  the  mouths  of  healthy  men,  namely,  Pneumococcus 
atypical  II,2  Type  III,  and  the  group  of.  microorganisms 
represented  by  Type  IV.  Pneumococcus  Type  I  was  en- 
countered in  only  a  few  instances  and  Type  II  was  not  found, 
although  these  two  microorganisms  are  responsible  for 
two-thirds  of  the  lobar  pneumonia  which  occurs  in  civil 
life. 


^•Report   of  the   Surgeon   General,   U.    S.   Army  to   the   Secretary   of   War,    1918,    p.   44. 
2Stillman,   F.   G. :     A   Study   of  Atypical   Type   II   Pneumococci,   Jour.   Exper.   Med.,    1919, 
xxix,   251. 

11 


12  INTRODUCTION 

During  the  investigation  at  ('amp  Funston  the  Commis- 
sion had  the  courteous  cooperation  of  Major  Willard  Stone, 
Director  of  Medical  Service,  and  received  much  valuable 
assistance  Prom  Lieutenant  A.  McGlory,  Registrar  of  the 
Base  Hospital. 

A  review  el'  the  accurately  compiled  records  of  the  base 
hospital  was  made  in  order  to  obtain  a  history  of  the  pneu- 
monias and  other  respiratory  diseases  which  had  occurred 
throughout  the  existence  of  the  camp,  established  in  Sep- 
tember, 1917.  It  soon  became  evident  that  a  disease  recog- 
nized as  influenza  had  been  prevalent  throughout  this  pe- 
riod and  its  incidence  had  shown  a  close  parallel  with  that 
of  acute  bronchitis.  At  the  same  time  there  had  been  much 
pneumonia  and  a  high  death  rate  from  this  disease.  The 
chart3  which  was  constructed  showed  that  the  disease  which 
had  been  designated  influenza  assumed  epidemic  propor- 
tions in  March,  1918.  Any  doubt  that  may  have  been  en- 
tertained concerning  the  nature  of  the  disease  is  dispelled 
by  the  characters  of  this  epidemic  which,  beginning  at  the 
end  of  February,  reached  its  height  on  March  12  and  rap- 
idly subsided;  1,127  men  with  influenza  entered  the  base 
hospital  between  March  4  and  March  29  and  many  more 
were  treated  in  the  infirmaries  of  the  camp.  In  April  there 
was  a  second  wave  of  influenza  and  in  May  a  third,  each  in 
large  part  limited  to  newly  drafted  men  brought  into  the 
camp  shortly  before  these  outbreaks.  Corresponding  to 
the  epidemic  of  influenza  there  was  a  great  increase  of 
pneumonia,  reaching  a  maximum  about  one  week  after  the 
height  of  the  incidence  of  influenza;  subsequently  the 
incidence  of  pneumonia  increased  after  each  one  of  the  sec- 
ondary waves  of  influenza.  Pneumonia  following  measles 
occurred  throughout  the  history  of  the  camp ;  in  November 
and  December,  1917,  there  was  a  severe  outbreak  of  pneu- 
monia following  measles  and  the  mortalitv  was  high.     Our 


3Opie,    E.    L.,    Freeman.    A.    \\\.    Blake,    F.    G.,    Small,   J.    C   Rivers,    T.    M. :      Pneumonia 
at  Camp  Funston,  Jour.   Am.   Med.   Assn.,   1919,   lxxii,   108. 


INTRODUCTION  1  3 

conclusions  in  regard  to  the  pneumonias  which  occurred 
during  the  history  of  Camp  Funston  were  as  follows: 

1.  Pneumonia  of  a  relatively  stationary  camp  popula- 
tion, such  as  that  which  occurred  among  white  troops  dur- 
ing the  period  of  our  investigation,  was  in  considerable 
part  caused  by  Pneumococcus  Types  I  and  II  and  resembled 
the  pneumonia  of  civil  life. 

2.  Pneumonia  of  newly  drafted  colored  troops  from 
southern  states  during  the  period  of  our  investigation  was 
caused  in  great  part  by  pneumococci  of  those  types  which 
occur  in  the  mouths  of  healthy  men,  namely,  Types  IV,  III 
and  atypical  II. 

3.  Pneumonia  caused  by  influenza  occurred  after  the  epi- 
demic of  influenza  which  we  have  described.  The  report 
states :  "With  the  information  available  it  is  not  possible  to 
draw  a  sharp  line  between  (1)  the  pneumonia  of  the  stable 
camp  population,  (2)  the  pneumonia  of  the  newly  drafted 
southern  troops,  and  (3)  the  pneumonia  following  influ- 
enza. It  is  possible  that  influenza,  in  greater  or  less  degree, 
also  acts  as  a  predisposing  factor  in  the  production  of  the 
first  and  second  varieties." 

4.  Pneumonia  with  measles  was  a  frequent  and  unusu- 
ally fatal  type  of  the  disease.  The  most  important  causes 
of  pneumonia  during  the  history  of  the  camp  were  influ- 
enza and  measles. 

Evidence  is  not  lacking  that  influenza  occurred  in  epi- 
demic form  in  other  widely  separated  camps  in  the  United 
States  during  the  spring  of  1918.  Vaughan  and  Palmer4 
state  that  a  disease  strongly  resembling  influenza  became 
prevalent  in  the  Oglethorpe  camps  about  March  18,  1918, 
and  continued  three  weeks;  during  this  time  the  number 
sent  to  hospital  or  to  quarters  with  this  disease  was  1,468 
in  a  total  strength  of  28,586.  Pneumonia,  does  not  appear 
to  have  followed  this  epidemic. 

*Vaughan,  V.  C,  and  Palmer,  G.  T.:  Communicable  Diseases  in  the  National  Guard 
and  National  Army  of  the  United  States,  Jour.  Lab.  and  Clin.  Med.,  1918,  iii, 
635. 


14  INTRODUCTION 

Miller  and  Lusk5  found  the  ordinary  type  of  pneu- 
monia prevalent  at  Camp  Dodge,  [owa,  until  March  is 
to  20,  L918,  when  abruptly  the  streptococcus  type  predomi- 
nated and  there  was  a  greal  increase  in  the  rate  of  mortal- 
ity. A  mild  tracheitis,  they  stale,  was  widespread  in  the 
camp  during  March. 

In  March.  1918,  one  member  of  our  commission  saw  an 
outbreak  of  influenza  at  Fort  Sam  Houston  which  was  iden- 
tical in  its  clinical  characters  with  the  disease  which  ap- 
peared as  a  pandemic  in  the  fall  of  1918. 

The  report  of  the  Surgeon  General6  lor  1919  shows  that 
there  was  a  sharp  increase  of  the  incidence  of  influenza  in 
the  army  during-  March,  reaching  a  maximum  in  April. 
The  rate  of  influenza  for  1,000  troops  fell  to  its  original 
level  through  May  and  June  and  finally  rose  to  a  great 
height  in  September  and  October. 

Influenza  in  epidemic  form  made  its  appearance  in  the 
army  camps  of  the  United  States  during  March,  1918.  The 
symptomatology  of  the  disease  associated  with  its  peculiar 
epidemiology  as  seen  at  Camp  Funston  make  its  recogni- 
tion  unquestionable.  The  disease  had  doubtless  been  pres- 
ent in  this  camp  since  its  establishment  in  September,  1917, 
hut  did  not  assume  epidemic  proportions  until  the  spring 
of  1919. 

Pneumonia  followed  the  epidemics  of  influenza  which  oc- 
curred in  the  spring  of  1918  and  exhibited  characters  sim- 
ilar to  those  of  the  pneumonias  which  followed  the  pan- 
demic of  September  and  October,  1918.  In  both  instances 
the  height  of  the  outbreak  of  pneumonia  has  been  one  week 
after  the  maximum  incidence  of  influenza. 

Influenza  became  epidemic  in  Spain  about  the  middle  of 
May  and  in  other  countries  received  the  name  "Spanish 
influenza"  which  is  not  more  applicable  than  the  designa- 
tion "Russian  influenza"  often  applied  to  the  disease  dur- 
ing the  pandemic  of  1889-90. 

•'.Miller,  J.   L.,   and   Lusk,   P.    B. :     Jour.    Am.    Med.    Assn.,    1918,    Ixxi,    702. 
"Report  of  the    Surgeon   General   to   the    Secretary    of   War,    1919,    i,   637. 


INTRODUCTION  1 5 

The  studies  of  MacNeal7  have  shown  that  the  first  epi- 
demic of  influenza  in  the  American  Expeditionary  Force  in 
France  occurred  about  April  15,  1918,  at  a  rest  camp  near 
Bordeaux,  reached  its  height  on  April  22  and  ceased  May 
5.  The  disease  was  of  a  mild  character  witli  few  complica- 
tions. Localized  epidemics  were  reported  from  various 
camps  and  hospitals  during  May  and  June,  when  the  dis- 
ease, MacNeal  states,  had  become  widespread  in  all  sections 
of  the  American  Expeditionary  Force  in  France  and  in  the 
French  and  British  armies  as  well.  Influenza  had  become 
epidemic  in  the  Italian  navy  in  the  first  two  weeks  of  May. 
The  belief  that  the  disease  was  introduced  from  America, 
the  author  thinks,  is  "  probably  completely  disproved  by 
the  fact  that  the  epidemic  was  subsequently  introduced  in- 
to America  in  August  and  September  and  found  there  a 
most  fertile  soil  for  its  spread."  This  view  is  disproved 
by  the  demonstration  that  influenza  had  appeared  as  scat- 
tered epidemics  in  the  army  camps  in  March,  1918.  There 
is  little  reason  to  doubt  that  influenza  in  the  American  Ex- 
peditionary Force  was  brought  from  America. 

At  the  end  of  August  our  commission  was  transferred 
from  Camp  Funston  to  Camp  Pike,  where  throughout  the 
history  of  the  encampment  pneumonia  had  been  so  prev- 
alent that  it  had  given  the  camp  the  rank  of  third  in  death 
rate  from  lobar  pneumonia  and  fourth  in  death  rate  from 
bronchopneumonia  among  32  camps  established  in  this 
country.  We  arrived  at  Camp  Pike  September  5  and  were 
stationed  at  the  base  hospital.  Our  work  was  facilitated 
by  the  hearty  cooperation  of  the  commanding  officer,  Major 
Morton  R.  Gibbons,  who  neglected  no  opportunity  to  pro- 
mote the  investigation.  Our  work  was  cordially  aided  by 
Major  Carl  R.  Comstock,  Director  of  the  Medical  Service, 
and  by  Major  Henry  H.  Lissner,  who  later  occupied  this  po- 
sition. Work  in  the  laboratory  of  the  hospital  received  the 
valuable  cooperation  of  Major  Allen  J.  Smith,  Director  of 

'MacNeal,    W.    J.:     The    Influenza    Epidemic    of    1918    in    the    American    Expeditionary 
Forces  in   France   and   England,   Arch.    Int.   Med.,    1919,    xxiii,    657. 


16  [NTRODUCTION 

the  Laboratory,  who  placed  at  our  disposal  every  facility 
available.  Lieutenant  James  R.  Davis,  who  was  for  a  time 
in  charge  of  the  laboratory,  effectively  assisted  the  work. 

The  commission  consisted  of  the  following  oi'licers:  E. 
L.  Opie,  Colonel,  M.  R.  C:  Allen  W.  Freeman,  Major,  M.  C; 
Francis  Gr.  Blake,  Major.  M.  R.  C,  James  C.  Small,  Lieu- 
tenant, M.  C.  and  Thomas  M.  Rivers,  Lieutenant,  M.  C. 
Major  Freeman  acted  as  epidemiologist  and  will  publish 
a  report  upon  the  epidemiology  of  Influenza  and  pneumonia 
at  Camp  Pike.  On  October  11  the  laboratory  car  "Lister" 
in  charge  of  Lieutenant  Warren  II.  Butz  was  assigned  to 
the  commission.  Lieutenant  Harry  1).  Bailey  was  attached 
to  the  commission  on  October  14  and  later  assisted  in  its 
work.  Valuable  technical  assistance  was  given  by  Ser- 
jeant Charles  Behre,  by  Wm.  E.  Hoy,  detailed  from  the 
Army  Medical  Museum,  and  by  Thomas  Payne. 

Study  of  the  pathology  of  the  lesions  concerned  was  com- 
pleted in  the  Pathological  Laboratory  of  Washington  Uni- 
versity School  of  Medicine. 

The  existence  of  an  epidemic  of  influenza  at  Camp  Pike 
was  recognized  on  September  23,  when  214  cases  of  influ- 
enza were  admitted  to  the  base  hospital.  Preceding  this 
date  and  beginning  September  1  there  had  been  a  gradual 
increase  of  the  number  of  patients  admitted  with  the  diag- 
nosis of  acute  bronchitis.  It  is  noteworthy  that  the  dem- 
onstration of  B.  influenzae  had  been  regarded  as  essential 
for  a  diagnosis  of  influenza  and  since  this  microorganism 
had  not  been  found,  instances  of  acute  inflammation  of  the 
respiratory  passages  with  the  symptoms  of  influenza  were 
classified  under  a  variety  of  names. 

After  September  2.')  influenza  was  recognized  by  its 
symptoms.  The  number  of  cases  increased  with  great  rapid- 
ity and  on  September  27  reached  over  1,000  per  day;  this 
number  was  approximately  maintained  during  one  week 
and  after  October  3  the  epidemic  gradually  subsided. 
Among  52,551  men  in  the  camp,  including  those  who  ar- 


INTRODUCTION 


17 


rived  during  October,  12,393  were  attacked  by  influenza ;  of 
these  1,499  suffered  with  pneumonia  and  466  died.  The 
height  of  the  outbreak  of  pneumonia  followed  approxi- 
mately one  week  after  that  of  influenza.  The  statistics  from 
September  20  to  October  14  collected  by  Major  Freeman 
show  that  pneumonia  following  influenza,  like  the  pneu- 
monia at  Camp  Funston  during  the  interepidemic  period, 
has  a  conspicuous  tendency  to  select  men  who  have  been  in 
the  camp  less  than  one  month,  designated  in  Table  I  as  new 
recruits : 

Table  I 


POPULA- 
TION 

INFLUENZA 

PNEUMONIA 

No. 

Per  cent 

No. 

Per  cent 

Men  in  camp  more  than 

one  month 
NeAv  recruits 

27,782 
23,769 

4,462 
7,263 

15.6 
30.6 

493 
1006 

1.7 

4.2 

Total 

51,551 

11,725 

22.7 

1499 

2.9 

New  recruits  were  nearly  two  and  a  half  times  as  sus- 
ceptible to  pneumonia  as  men  who  had  been  in  camp  more 
than  one  month.  This  statement  does  not  take  into  con- 
sideration differences  in  the  environment  and  mode  of  liv- 
ing of  the  new  men. 

In  view  of  the  existing  uncertainty  concerning  the  bacte- 
riology of  influenza  and  its  associated  pneumonias,  the  com- 
mission has  availed  itself  of  the  opportunity  afforded  by 
the  epidemic  of  influenza  to  determine  what  bacteria  were 
present  in  the  nasopharynx  and  sputum  in  these  diseases. 
The  examinations  have  been  necessarily  limited  to  a  small 
proportion  of  the  immense  number  of  patients  admitted  to 
the  hospital  with  influenza  and  pneumonia.  Autopsies  on 
those  who  have  died  with  pneumonia  have  offered  a  more 
direct  means  of  determining  the  relation  of  bacteria  to  in- 
flammation of  the  bronchi  and  lungs.  An  attempt  has  been 
made  to  classify  the  pneumonias  following  influenza  and  to 
determine  their  relation  to  the  complex  bacterial  flora  of 
the  injured  respiratory  passages.  These  studies  have 
shown  very  early  the  threatening  prevalence  of  strepto- 


L8  [NTRODUCTION 

coccus  pneumonia,  and  appropriate  measures  have  been 
taken  to  combat  the  spread  of  this  infection.  No  better  il- 
lustration could  be  furnished  to  demonstrate  the  value  of 
routine  performance  of  autopsies  as  a  means  for  the  recog- 
nition of  obscure  epidemic  disease. 

In  view  of  the  wide  di I't'ereiiee  of  opinion  concerning  the 
pathology  of  influenzal  pneumonia  special  study  lias  been 
given  to  the  lesions  of  the  disease,  because  the  epidemic  lias 
furnished  the  unique  opportunity  of  examining  all  in- 
stances of  pneumonia  accurately  referable  to  an  epidemic 
of  influenza  attacking  a  Large  but  definitely  defined  group 
of  individuals  (50,000  troops).  In  a  civil  hospital  there  is 
often  great  difficulty  in  deciding,  even  in  the  presence  of  an 
epidemic,  if  death  from  pneumonia  is  the  result  of  influ- 
enza, but  at  Camp  Pike  the  relation  of  the  heightened  death 
rate  to  the  epidemic  lias  excluded  all  save  a  trivial  error  in 
determining  the  relation  of  fatal  pneumonia  to  influenza. 

At  the  direction  of  Col.  F.  F.  Russell,  who  has  promoted 
the  work  of  the  commission  by  unfailing  aid,  a  special 
study  has  been  made  of  the  relation  of  hemolytic  strepto- 
coccus to  the  complications  of  measles. 

During  the  later  period  of  the  investigation  at  Camp  Pike 
experiments  were  performed  on  monkeys  to  determine  the 
pathogenicity  of  B.  influenza1  and  of  microorganism  isolated 
from  the  pneumonias  following  influenza.  Typical  lobar 
pneumonia  was  produced  in  monkeys  by  intratracheal  in- 
jection of  pneumococci.  These  experiments  are  described 
in  an  appendix. 

The  Surgeon  General  lias  approved  the  publication  of  this 
report  but  the  authors  alone  are  responsible  for  the  views 
expressed. 

Eugene  L.  Opie. 

Washington  University 
School  of  Medicine 


CONTENTS 


CHAPTER  I  page 

The  Etiology  of  Influenza.     (By  Francis  G.  Blake,  M.D. ;   Thomas 

M.  Rivers,  M.D.;  James  C.  Small,  M.D.) 25 

Discussion,  43;   Conclusions,  49. 


CHAPTER  II 

Clinical  Features  and  Bacteriology  of  Infuuenza  and  Its  Associ- 
ated Purulent  Bronchitis  and  Pneumonia.  (By  Francis 
G.  Blake,  M.D.,  and  Thomas  M.  Rivers,  M.D.) 51 

Influenza,  52;  Purulent  Bronchitis,  56;  Pneumonia,  59;  Hemolytic 
Streptococcus  Pneumonia  Following  Influenza,  70;  Bacillus  Influenzas 
Pneumonia   Following  Influenza,   72;    Summary,    73;    Discussion,    76. 


CHAPTER  III 

Secondary  Infection  in  the  Ward  Treatment  of  Influenza  and 
Pneumonia.  (By  Eugene  L.  Opie,  M.D. ;  Francis  G.  Blake, 
M.D. ;  James  C.  Small,  M.D. ;  and  Thomas  M.  Rivers,  M.D.)     .     83 

Secondary  Infection  with  S.  Hemolyticus  in  Pneumonia,  84;  Second- 
ary Infection  with  Pneumococcus  in  Pneumonia,  91 ;  Secondary  Con- 
tact Infection  in  Influenza,  95;  Methods  for  the  Prevention  of 
Secondary  Contact  Infection  in  Influenza  and  Pneumonia,  98 ;  Sum- 
mary, 106. 

CHAPTER  IV 

The  Pathology  and  Bacteriology  of  Pneumonia  Following  Influ- 
enza. (By  E.  L.  Opie,  M.D.;  F.  G.  Blake,  M.D.;  and  T.  M. 
Rivers,  M.D.) 107 

Bronchitis,  142;  Lobar  Pneumonia,  154;  Bronchopneumonia,  162; 
Peribronchial  Hemorrhage  and  Pneumonia,  189 ;  Suppurative  Pneu- 
monia with  Necrosis  and  Abscess  Formation,  199;  Interstitial  Sup- 
purative Pneumonia,  209 ;  Suppurative  Pneumonia  with  Multiple  Clus- 
tered Abscesses  Caused  by  Staphylococci,  225;  Empyema,  Pericarditis 
and  Peritonitis,  232;  Bronchiectasis,  239;  Unresolved  Bronchopneumo- 
nia, 261. 

19 


L1!)  CONTEXTS 

CHAPTER  V 

i'akv    Infection    in   the   Ward    Treatment   of    Measles.      (By 
James    C.    Small,    RID.) 282 

Eemolytic  Streptococci  with  Measles  al  Camp  Pike,  297;  Complica- 
tions of  Measles,  303;  Tlio  Dissemination  of  Eemolytic  Streptococci 
in  Wards,  315;  Carriers  of  Eemolytic  Streptococci,  321. 

CHAPTEB  VI 

The  Pathology  and  Bacteriolog's  of  Pneumonia  Following  Measles. 
(By  Eugene  L.  Opie,  M.D.;  Francis  G.  Blake,  M.D.;  James 
C.  Small,  M.D.;  and  Thomas  M.  Rivers,  M.D.) 234 

Changes  in  Bronchi,  336;  Lobar  Pneumonia,  337;  Bronchopneumonia, 
340;  Suppurative  Pneumonia,  .'147;  Pneumonia  Associated  with  Acute 
Infectious  Diseases  other  than   Influenza   and  Measles,  353. 

CHAPTER  VII 

Summary  of  the  Investigation  and  Conclusions  Reached.  (By  Eu- 
gene L.  Opie.  M.D.) ' 359 

Lobar  Pneumonia,  3(52;  Bronchopneumonia,  363 ;  Streptococcus  Pneu- 
monia, 36.1;  Staphylococcus  Pneumonia,  3(56;  Empyema,  366;  Bron- 
chiectasis, 367;  Unresolved  Bronchopneumonia,  368;  B.  Influenza?, 
369;  Pneumococcus,  372;  S.  Hemolyticus,  374;  Nonhemolytic  Strep- 
tococci, 376;  Staphylococci,  377;  Pneumonia  of  Measles,  378;  The 
Transmission  of  Streptococcus  Pneumonia,  381;  Transmission  of 
Pneumococcus  Pneumonia,  383;  Prevention  of  the  Transmission  of 
Pneumonia,  3S3. 

APPENDIX 

Experimental  Inoculation  of  Monkeys  with  Bacillus  Influenzae 
and  Microorganisms  Isolated  from  the  Pneumonias  of  In- 
fluenza. (By  Eugene  L.  Opie,  M.D. ;  Allen  W.  Freeman, 
M.D. ;  Francis  G.  Blake,  M.D. ;  James  C.   Small,  M.D.;  and 

Thomas    M.    Rivers,    M.D.) 387 

Inoculation  of  the  Nose  and  Pharynx  with  B.  Influenzas,  3S9 ;  Intro- 
duction of  Bacillus  Influenza?  into  the  Trachea,  391;  Introduction  of 
B.  Influenza?  and  S.  Hemolyticus  into  the  Trachea,  392;  Introduction 
of  B.  Influenza?  and  of  Pneumococcus  or  of  Pneumococcus  Alone  into 
the  Trachea,  393. 


ILLUSTRATIONS 

CHARTS  PAGE 

1.  The  onset  of  cases  of  pneumonia  shown  by  autopsy  to   be  uncompli- 

cated by  secondary  infection  with  hemolytic  streptococcus  and  of 
cases    of   streptococcus    pneumonia        141 

2.  The  date  of  onset  of  cases  in  which  autopsy  demonstrated  lobar  pneu- 

monia      161 

3.  Shows  the  relation  of  the  epidemic  of  measles  to  that  of  influenza  at 

Camp  Pike,  and  the  relations  of  the  pneumonia  following  measles 

to   both   measles   and   influenza 293 

4.  Shows  the  time  interval  between  the  onset  of  measles  and  the  onset  of 

the  subsequent  pneumonia  in  the  56  cases  of  pneumonia  follow- 
ing  measles    at    Camp    Pike 306 

5.  Shows  the  time  relation  between  the  identification  of  hemolytic  strep- 

tococci in   the   throats   and   the   development   of   otitis   media   in 

27  cases  shown  to  be  due  to  hemolytic  sti'eptococci 314 

FIG. 

1.  Acute  bronchitis  showing  engorgement  of  blood  vessels  of  mucosa  and 

elevation  of  epithelium  by  serum  and  blood 146 

2.  Acute  bronchopneumonia  with  nodules  of  peribronchiolar  consolidation 

and  purulent  bronchitis 167 

3.  Acute  bronchopneumonia  with  peribronchiolar  consolidation     ....  169 

4.  Acute    bronchopneumonia    with    peribronchiolar    consolidation     .     .     .170 

5.  Bronchopneumonia  with   hemorrhagic   peribronchiolar   consolidation     .  174 

6.  Acute  bronchopneumonia  with  confluent  gray  lobular  consolidation  in 

lower  part  of  upper  lobe  and  hemorrhagic  peribronchiolar  pneu- 
monia in  lower  lobe;  purulent  bronchitis ISO 

7.  Bronchopneumonia  with  purulent  bronchitis  and  peribronchial  hemor- 

rhage       190 

8.  Streptococcus  pneumonia  with  massive  necrosis 201 

9.  Abscess   below   pleura   with    perforation    caused    by   hemolytic    strep- 

tococci      202 

10.  Interstitial  suppurative  pneumonia;  interstitial  septa  are  the  site  of 

suppuration   and  lymphatics   are   distended  with  purulent  fluid; 
empyema 211 

11.  Suppurative    interstitial    pneumonia 212 

12.  Suppurative     interstitial     pneumonia 216 

13.  Suppurative  interstitial  pneumonia  showing  a  dilated  lymphatic     .     .  217 

21 


22  ILLUSTRATIONS 

no.  page 

ll.  Endophlebitis  occurring  in  association  with  suppurative  pneumonia     .  219 

15.  Abscesses  in  two  clusters  caused  by  S.  aureus  in  upper  part  of  right 

upper  lobe 227 

16.  Abscesses  in  cluster  caused  by  s.  aureus  ;it  apex  of  right  lulu'    .    .     .  228 

17.  Acute  bronchiectasis  showing  fissures  penetrating  into  bronchial  wall 

and  at  one  place  entering  alveolar  tissue 24(> 

IS.  Acute  bronchiectasis  showing-  fissures  in   the   bronchial  wall  extending 

into  neighboring  alveoli  which  in  zone  about  are  filled  with  fibrin  247 

19.  Acute  bronchiectasis;  the  bronchial  wall  indicated  by  engorged  mucosa 

shows  a  varying  degree  of  destruction,  fissures  extending  into  and 
through  the  bronchial  wall 248 

20.  Acute  bronchiectasis  with  destruction  of  bronchial  wall  exposing  alve- 

oli filled  with  fibrin 249 

21.  Bronchiectasis  with  fissures  extending  through  the  bronchial  wall  into 

alveolar  tissue  which  is  site  of  fibrinous  pneumonia 251 

22.  Regeneration   of   epithelium    over  fissures  which   have   been   formed   in 

the   wall   of  a  bronchus 252 

23.  Squamous  epithelium  growing  over  the  defect  in  the  bronchial   wall      .   253 

24.  Acute   bronchiectasis   with   fissures   extending   through    bronchial    wall 

which  is  marked  by  great  engorgement   of  blood  vessels     .     .     .  25-1 

25.  Advanced   bronchiectasis    throughout    lower   left    lobe 258 

26.  Unresolved  bronchopneumonia   with  tubercle-like  nodules  of  peribron- 

chiolar consolidation  best  seen  in  lower  lobe ;  bronchiectasis     .     .  2(iS 

27.  Unresolved  pneumonia  with  peribronchial  formation  of  fibrous  tissue; 

bronchiectasis 270 

28.  Unresolved  pneumonia  with  bronchiectasis  showing  new  formation  of 

fibrous  tissue  about  a  greatly  dilated  bronchus  of  which  the  epi- 
thelial   lining    has    been    lost 271 

29.  Lobar   pneumonia   following   measles 338 

30.  Unresolved  bronchopneumonia  with  measles  showing  new  formation  of 

fibrous    tissue    about    a    bronchus    and    in    immediately    adjacent 
alveolar     walls 342 

31.  Unresolved    bronchopneumonia    with    measles    showing    a    nodule    of 

chronic  fibrous  pneumonia  surrounding  a  respiratory  bronchiole     .  343 

32.  Unresolved    bronchopneumonia    with    measles    showing    chronic    pneu- 

monia  about  a  respiratory  bronchiole  and  alveolar  duct     .     .     .344 

33.  Experimental  lobar  pneumonia   in  the  stage  of  gray  hepatization  pro- 

duced by  injection  of  Pneumococcus  III  into  the  trachea  of  a 
monkey 395 


EPIDEMIC  RESPIRATORY  DISEASE 


EPIDEMIC  RESPIRATORY  DISEASE 

THE  PNEUMONIAS  AND  OTHER  INFECTIONS  OF  THE 
RESPIRATORY  TRACT 
ACCOMPANYING  INFLUENZA  AND  MEASLES 


CHAPTER  I 

THE  ETIOLOGY  OF  INFLUENZA 

Feancis  G.  Blake,  M.D. ;  Thomas  M.  Rivers,  M.D. ;  James 

C.  Small,  M.D. 

The  bacteriologic  investigation  which  will  be  described 
was  made  at  Camp  Pike,  Arkansas,  during  the  period  of 
the  influenza  epidemic  from  September  6  to  December  5, 
1918.  The  data  presented  are  limited  to  observations  made 
during  life  in  uncomplicated  cases  of  influenza  and  to  con- 
trol studies  in  normal  individuals,  and  in  cases  of  measles. 
Bacteriologic  studies  made  at  autopsy  will  be  described 
in  a  subsequent  part  of  this  report. 

Because  of  the  wide  variations  in  opinion  concerning  the 
relationship  of  various  bacteria  to  influenza  that  have 
arisen  during  the  progress  of  the  recent  pandemic,  a  brief 
review  of  the  salient  features  of  the  earlier  literature  seems 
advisable.  In  1892  Pf eiffer1  found  a  small,  Gram-negative, 
hemophilic  bacillus  in  all  cases  of  influenza,  often  in  almost 
pure  culture,  both  during  life  and  at  autopsy.  He  stated 
that  the  organism  was  found  only  in  cases  of  influenza  or 
in  those  convalescent  from  the  disease.  Similar  bacilli  oc- 
casionally found  in  other  conditions  he  classified  as  pseudo- 
influenza  bacilli.  He  furthermore  showed  that  freshly  iso- 
lated cultures  were  pathogenic  for  monkeys,  producing  a 
disease  not  unlike  influenza,  though  lacking  in  what  he  con- 

iPfeiffer:     Ztschr.    f.   Hyg.,    1893,   xiii,   357. 

25 


26        PNEUMONIAS  AND   [NFECTIONS  OF   aESPIRATOR"X  TRACT 

sidered  the  characteristic  lung-  lesions.  [To  therefore  felt 
justified  in  claiining  that  this  bacillus,  which  he  designated 
I').  influenza1,  was  the  cause  of  epidemic  influenza.  Pfeif- 
I'er's  work^though  hailed  by  many  as  unassailable,  lias 
failed  to  stand  the  test  of  time  in  two  respects.  It  has  been 
definitely  shown,  by  Wollstein2  in  particular,  that  there  is 
no  justification  for  recognizing  a  group  of  pseudoinfluenza 
bacilli,  organisms  so  classified  by  Pfeiffer  being  indistin- 
guishable from  B.  influenza1.  Furthermore,  numerous  in- 
vestigations have  demonstrated  that  B.  influenza}  may  fre- 
quently be  found  in  a  variety  of  diseases  affecting  the  res- 
piratory tract  and  in  a  small  proportion  of  normal  individ- 
uals. Kretz3  found  it  47  times  in  950  examinations,  usually 
associated  with  disease  of  the  respiratory  tract.  Siiss- 
wein,4  Liebscher,5  Jehle,G  Wollstein,2  Davis7  and  many 
others  have  demonstrated  its  presence  in  cases  of  measles. 
Lords  isolated  B.  influenzae  in  30  per  cent  of  186  sputums 
from  patients  with  acute  and  chronic  infection  of  the  res- 
piratory tract.  Boggs9  found  it  in  frequent  association 
with  chronic  bronchiectasis.  Wollsteim2' 10  showed  that  it 
was  often  present  in  the  respiratory  diseases  of  infants, 
and  was  not  an  infrequent  cause  of  meningitis.  Rosenthal11 
found  that  one  in  six  of  normal  individuals  harbors  influ- 
enza bacilli  and  therefore  considered  it  purely  a  sapro- 
phyte, a  position,  of  course,  thoroughly  untenable  in  the 
face  of  indisputable  evidence  that  it  may  be  highly  patho- 
genic. The  widely  accepted  statement  that  B.  influenzas  is 
nonpathogenic  for  animals  has  apparently  served  in  con- 
siderable degree  to  shake  belief  in  its  etiologic  relationship 
to  epidemic  influenza.  It  would  appear,  however,  that  this 
opinion  is  not  founded  upon  fact.    Reference  is  again  made 


:Wollstein:     Jour.    Exper.    Med.,    1916,    viii.    681. 
•Kretz:     Wien.  klin.   Wchnschr.,   1897,  x,  877. 
*Suss\vein:     WTien.   klin.    Wchnschr.,    1901,    xiv,    1149. 
^Liebscher:      Prag.   med.    Wchnschr..    1903,   xxviii,   85. 
"Jehle:     Ztschr.   f.    Heilk.,    1901,   xx,    n.    s.    2,    Int.    Med. 
7Davis:     Jour.    Infect.    Dis.,    1906,   iii.    1. 
8Lord:     Boston   Med.    Sur.   Jour.,    1905,    clii,    537,    574. 
"Boggs:     Am.  Jour.   Med.    Sc,    1905,   cxxx,   902. 
"Wollstein:     Am.   Jour.    Dis.    Child.,    1911,   i,   42. 
"Rosenthal:     Comp.   rend.   Soc.   Biol.,    1903,  lv,   1500. 


ETIOLOGY  OF    I  X  FLU  E  X  Z  A  27 

to  the  work  of  Wollstein12,  who  has  shown  that  virulent 
strains  of  B.  influenzae,  when  freshly  isolated  from  the  hu- 
man host,  are  highly  pathogenic  for  rabbits  and  monkeys 
and  that  nearly  all  strains  are  more  or  less  pathogenic  for 
mice  and  guinea-pigs. 

None  of  these  modifications  of  Pfeiffer's  original  work, 
however,  would  seem  to  constitute  any  valid  reason  for 
abandoning  the  conception  of  the  etiologic  importance  of 
B.  influenzae.  On  the  contrary,  they  are  quite  in  harmony 
with  well-established  facts  concerning  other  bacteria  which 
cause  infections  of  the  respiratory  tract.  Such  bacteria  are 
frequently  found  in  normal  individuals  leading  a  sapro- 
phytic existence,  are  often  associated  with  other  disease 
conditions,  and  tend  to  show  marked  variations  in  viru- 
lence. 

Since  the  outbreak  of  scattered  epidemics  of  influenza 
beginning  in  1915-16,  which  finally  culminated  in  the  pan- 
demic of  1918-19,  a  vast  amount  of  literature  on  the  subject 
has  appeared.  No  attempt  has  been  made  thoroughly  to 
analyze  this,  because  much  of  it  is  not  available,  much  of 
it  abounds  in  contradictions  which  it  is  difficult  to  harmo- 
nize at  the  present  time,  and  much  of  it  has  been  written  on 
the  basis  of  insufficient  data  gathered  under  the  handicap 
of  war  conditions  by  men  without  sufficient  time  to  under- 
take special  investigation,  or  it  is  feared,  in  many  instances, 
not  sufficiently  qualified  by  previous  bacteriologic  training. 

The  sum  and  substance  of  opinion  in  1918  would  seem  to 
be  best  summarized  by  quoting  from  the  published  report 
compiled  by  the  British  Medical  Research  Commission:13 
"Although  Pfeiffer  may  yet  furnish  reasons  why  the  ver- 
dict should  not  be  pronounced,  there  is  already  sufficient 
material  to  shake  the  orthodox  conception  out  of  its  high 
altar.  Two  facts  stand  out  prominently :  the  generally  ac- 
knowledged, or  by  some  reluctantly  admitted,  absence  of 
B.  influenzae  from  organs  on  postmortem  examinations,  and 

"Wollstein:        Tour.    Exper.    Med.,    1915,    xxii,    445. 

"Med.   Sup.    October   1,    1918   also  Jour.   Am.   Med.    Assn.,    1918,   lxxi,    1573. 


28        PNEUMONIAS  AND   [NFEOTIONS  OF   RESPIRATORY  TRACT 

the  universally  recorded  findings  of  diplostreptococci,  sin- 
gly or  in  association  with  the  Pf eiffer  bacillus. "  Comment 
on  this  opinion  will  be  made  in  the  general  discussion  at 
the  end  of  this  paper. 

In  undertaking  a  study  of  the  bacteriology  of  influenza, 
it  seemed  essential  to  bear  in  mind  certain  clinical  features 
of  the  disease  which  will  be  discussed  in  greater  detail  in  a 
subsequent  paper.  It  suffices  to  say  for  our  present  pur- 
pose that  it  is  felt  that  influenza  in  itself  should  be  regarded 
as  a  self-limited  disease  of  short  duration  (two  to  five  days 
in  most  instances),  the  most  prominent  local  manifestation 
of  which  is  a  rapidly  progressing  attack  upon  the  mucous 
membranes  of  the  respiratory  tract.  Among  the  cases  ob- 
served during  the  epidemic  at  Camp  Pike  uncomplicated 
influenza  never  proved  fatal  and  death  invariably  was  as- 
sociated with  a  complicating  pneumonia.  In  a  large  ma- 
jority of  cases  pneumococci,  S.  hemolyticus,  or  less  fre- 
quently other  bacteria  in  addition  to  B.  influenza?  were  asso- 
ciated with  the  pneumonia.  11  is  1'elt,  therefore,  that  in 
any  attempt  to  determine  the  primary  cause  of  influenza 
bacteriologic  studies  made  during  life  in  early  uncompli- 
cated cases  of  the  disease  are  of  primary  importance  and 
that  the  bacteriology  of  the  sputum  of  patients  with  com- 
plicating pneumonia  and  the  bacteriology  of  autopsies  can 
only  properly  be  used  as  valuable  supplements  to  data  so 
obtained. 

Since  cultures  from  the  respiratory  tract  must  often  of 
necessity  contain  many  bacteria  which  play  no  part  in  the 
production  of  influenza,  it  is  essential  to  have  a  working 
knowledge  of  the  bacteria  that  may  be  encountered  by  the 
methods  employed.  It  is  also  important  that  such  knowl- 
edge as  may  have  been  gained  in  interepidemic  periods  be 
amplified  by  study  of  the  bacterial  flora  present  at  various 
periods  throughout  the  course  of  an  epidemic,  both  in  nor- 
mal individuals  and  in  other  disease  conditions.  These 
points  have  been  borne  in  mind  throughout  the  present 


ETIOLOGY  OF  INFLUENZA  29 

study  and  such  observations  have  formed  an  essenital  part 
of  the  work. 

Methods. — In  an  investigation  of  this  nature  the  culture 
methods  employed  should  be  suitably  directed  to  determine 
primarily  what  bacteria  are  present  and  in  what  relative 
proportion  they  exist.  The  use  of  culture  or  animal  inoc- 
ulation methods  that  are  highly  selective  in  character,  en- 
hancing the  growth  of  certain  bacteria  and  retarding  or  in- 
hibiting the  growth  of  others,  are  of  great  additional  value, 
but  can  only  properly  be  used  secondarily  in  order  to  aug- 
ment the  results  obtained  by  nonselective  culture  methods. 
As  the  most  suitable  medium  for  the  purpose  in  hand  plain 
meat  infusion  agar,  titrating  0.1  +  to  0.3  +  to  phenolphtha- 
lein,  to  which  5  per  cent  of  sterile  defibrinated  horse  blood 
was  added,  was  used.  Since  growth  on  freshly  poured 
plates  is  greatly  superior  to  that  on  plates  that  have  been 
stored,  the  agar  was  melted  as  needed,  the  blood  being- 
added  when  the  medium  had  cooled  to  approximately  45° 
C.  Cultures  from  the  nose  and  throat  were  made  by  swab- 
bing the  mucous  membranes  with  a  sterile  applicator, 
touching  the  applicator  to  a  small  area  on  the  surface  of  a 
blood  agar  plate,  and  spreading  the  inoculum  over  the  sur- 
face of  the  medium  with  a  platinum  needle,  insuring  as 
wide  a  separation  as  possible.  Direct  cultures  of  selected 
and  washed  specimens  of  sputum  were  made  when  possi- 
ble. In  many  instances,  of  course,  it  was  impossible  to  get 
sufficiently  satisfactory  specimens  to  permit  of  washing, 
especially  when  cultures  were  made  very  early  in  the  dis- 
ease. To  supplement  direct  culture  of  the  sputum  the 
mouse  inoculation  method  as  employed  for  the  determina- 
tion of  pneumococcus  types  was  used.  This  is,  of  course, 
a  highly  selective  method,  of  particular  value  in  the  detec- 
tion of  pneumococcus  and  B.  influenzae  when  they  are  pres- 
ent in  relatively  small  numbers  as  compared  with  other 
bacteria.     Plates  were  examined  after  twenty  to  twenty- 


30        PNEUMONIAS  AND   [NFECTIONS  OE   RESPIRATOR'S  TRACT 

four  hours'  incubation  and  again  at  the  end  of  thirty-six 
in  Forty-eight  hours  when  necessary. 

In  the  presenl  study,  attention  has  been  centered  upon 
P>.  influenzae,  S.  hemolyticus,  and  the  various  immunologic 
types  of  piit'uiiiococci,  other  organisms  encountered  having 
played  no  significant  part  in  the  cases  studied  except  in  rare 
instances.  B.  influenzae  was  identified  by  its  morphologic, 
staining  and  cultural  characteristics  and  conformed  to  the 
classical  description  given  by  Pfeiffer.  S.  hemolyticus  was 
identified  by  its  morphologic,  staining,  and  cultural  char- 
acteristics on  blood  agar,  supplemented  by  a  confirmatory 
hemolytic  test  with  washed  sheep  corpuscles,  and  bile  sol- 
ubility test.  Pneumococci  were  identified  by  morphologic, 
staining  and  cultural  characteristics,  bile  solubility  test,  and 
agglutination  with  specific  antipneumococcus  immune  sera. 
Note  was  made  in  most  instances  of  the  presence  of  other 
organisms,  such  as  members  of  the  Gram-negative  diploeoc- 
cus,  staphylococcus,  diphtheroid  and  streptococcus  viridans 
groups,  but  no  attempt  was  made  further  to  isolate  or  iden- 
tify them. 

Bacillus  Influenzae  in  Cases  of  Influenza. — On  October  10, 
1918,  at  the  height  of  the  epidemic  at  Camp  Pike,  search  for 
B.  influenza?  was  made  in  a  group  of  23  consecutive  cases  of 
uncomplicated  influenza  from  one  to  six  days  after  the  on- 
set of  the  disease.  From  each  individual  simultaneous  cul- 
tures on  blood  agar  plates  were  made  (a)  from  the  nose, 
(b)  from  the  throat,  and  (c)  from  the  sputum,  and  the  spu- 
tum from  each  case  was  injected  into  the  peritoneal  cavity 
of  a  white  mouse.  A  similar  study  of  5  consecutive  cases 
was  made  on  November  19.  The  results  are  presented  in 
Table  II. 

By  means  of  multiple  cultures  taken  simultaneously  from 
different  portions  of  the  respirator)'  tract  no  difficulty  was 
encountered  in  demonstrating  B.  influenzae  in  all  these  cases 
of  uncomplicated  influenza.  Not  only  was  B.  influenzae 
found  in  all  cases,  but  often  in  very  large  numbers  predom- 


.ETIOLOGY  OF  INIO.UKNZA 


31 


mating  over  all  other  bacteria  on  at  least  one  of  the  plates 
from  each  patient,  and  in  occasional  instances  occurring  in 
nearly  pure  culture.  One  culture  made  about  two  hours 
after  onset  of  the  initial  coryza  is  of  interest.  There  was 
at  the  time  a  profuse  serous  nasal  discharge.    One  drop  of 


Table  II 
Presence  op  B.  Influenzae  in  28  Cases   of  Influenza 


SPUTUM 

DAY  OF 

SPUTUM 

PASSED 

NO. 

DISEASE 

NOSE 

THROAT 

CULTURE 

THROUGH 
MOUSE 

1 

1 

+ 

+ 

+ 

+ 

2 

4 

- 

+ 

+ 

+ 

3 

5 

- 

- 

+ 

- 

4 

4 

- 

- 

+ 

+ 

5 

3 

- 

- 

+ 

+ 

6 

4 

- 

+ 

+ 

C 

7 

2 

- 

+ 

- 

c 

8 

4 

+ 

+ 

+ 

- 

9 

5 

- 

+ 

+ 

+ 

10 

2 

+ 

- 

- 

- 

11 

2 

- 

+ 

C 

+ 

12 

3 

C 

+ 

+ 

+ 

13 

3 

- 

_ 

_ 

+ 

14 

o 

- 

- 

+ 

+ 

15 

3 

c 

- 

- 

+ 

16 

1 

- 

+ 

+ 

+ 

17 

3 

- 

+ 

- 

+ 

18 

4 

+ 

+ 

c 

+ 

19 

6 

- 

- 

+ 

+ 

20 

1 

- 

+ 

+ 

+ 

21 

2 

- 

+ 

- 

+ 

22 

4 

+ 

_ 

+ 

+ 

23 

3 

c 

- 

— 

+ 

24 

2 

+ 

- 

_ 

_ 

25 

1 

- 

- 

+ 

+ 

26 

5 

- 

- 

+ 

+ 

27 

1 

- 

+ 

- 

+ 

28 

1 

- 

- 

+ 

+ 

6 

14 

17 

22 

c   indicates   that   the  plate  was   contaminated. 

this  allowed  to  fall  on  the  surface  of  a  blood  agar  plate 
gave  a  practically  pure  culture  of  B.  influenza?. 

During  the  latter  part  of  November  and  in  early  Decem- 
ber a  small  secondary  wave  of  influenza  occurred  at  Camp 
Pike.  In  a  series  of  48  consecutive  cases,  B.  influenzae  was 
readily  found  in  all  by  means  of  combined  throat  cultures 


QO 


pneumonias  and  infections  of  inspiratory  tract 


and  mouse  inoculation  of  the  sputum,  33  times  ((IS. 7  per 
cent)  in  the  throat  cultures,  39  times  (81.3  per  cent)  in  the 
sputum.  These  cases  were  cultured  on  admission  to  the 
receiving  ward  of  the  hospital  within  twenty-four  to  forty- 
eighl  hours  after  onset  and  were  all  early  cases  of  influenza 
without  complications  at  the  time  the  cultures  were  made. 
In  90  more  consecutive  cases  in  this  series  62  or  68.9  per 
cent  showed  B.  influenza  in  a  single  throat  culture  taken 
on  admission. 

A  summary  of  all  cultures  made  in  cases  of  uncomplicated 
influenza  is  presented  in  Table  III. 

Of  any  single  method  used  the  intraperitoneal  inocula- 
tion of  a  white  mouse  with  a  specimen  of  the  patient's  spu- 


Table  hi 
Presence  of  B.  Influenza  in  Cases  of    Influenza 


METHOD 

NUMBER   OF 
CASES  CULTURED 

B.    INFLUENZA    FOUND 

NUMBER 

PER   CENT 

Xose   culture 

28 

6 

21.4 

Throat  culture 

166 

109 

65.7 

Sputum  culture 

28 

17 

60.7 

Sputum  (mouse  passage) 

76 

61 

80.3 

Combined  nose,  throat  and 

sputum    cultures   and 

sputum  inoculation 

28 

28 

100 

Combined   throat    cultures 

and  sputum  inoculation 

48 

48 

100 

turn  proved  the  most  efficient  in  demonstrating  the  presence 
of  B.  influenzae.  No  single  method  served  to  demonstrate 
B.  influenzae  in  all  cases,  but  by  simultaneous  cultures  from 
the  nose,  throat,  and  deeper  air  passages  no  difficulty  was 
met  in  showing  that  B.  influenzae  was  invariably  present, 
usually  in  abundance  somewhere  in  the  respiratory  tract 
during  the  acute  stage  of  the  disease.  This  result  is  not 
out  of  harmony  with  the  rapidly  progressive  character  of 
the  attack  upon  the  mucous  membranes  of  the  respiratory 
tract  in  influenza. 

Of  interest  in  this  connection  are  certain  observations 
which  suggest  that  the  presence  of  B.  influenzae  in  predomi- 


ETIOLOGY   OF    IXI'r/CKNXA  66 

nant  numbers  at  least  is  in  many  eases  coincident  with  the 
acute  stage  of  influenza  and  that  the  organisms  show  a  tend- 
ency rapidly  to  diminish  in  abundance  with  the  progress 
of  the  disease  to  recovery.  In  82  cases  of  influenza  cultured 
on  the  day  of  admission  to  the  hospital,  B.  influenzae  was 
present  in  52  (63.4  per  cent)  of  the  throat  cultures.  Re- 
peated throat  cultures  in  this  group  of  cases  from  the 
fourth  to  the  eighth  day  after  admission  when  the  temper- 
ature had  fallen  to  normal,  showed  that  B.  influenzae  was 
still  present  in  demonstrable  numbers  in  the  throat  of  only 
25  cases  or  30.5  per  cent.  Not  only  was  there  a  material 
reduction  in  the  number  of  patients  in  whom  B.  influenzas 
could  be  demonstrated  by  the  throat  culture  method,  but 
the  contrast  in  the  predominance  of  B.  influenzae  on  the 
plates  made  early  in  the  disease  with  those  made  during 
convalescence  was  often  very  striking.  It  is  only  fair  to 
say,  however,  that  some  cases  continued  to  carry  B.  influ- 
enzae in  their  throats  in  large  numbers  throughout  the  pe- 
riod of  observation. 

Presence  of  Pneumococcus  in  Cases  of  Influenza. — It 
seemed  of  some  importance  to  determine  the  prevalence  of 
pneumococcus  in  cases  of  influenza,  not  because  of  any  pos- 
sibility that  pneumococci  might  bear  an  etiologic  relation- 
ship to  the  disease,  but  more  by  way  of  comparison  with  the 
prevalence  of  B.  influenzae,  since  both  organisms  are  found 
in  the  mouths  of  normal  individuals  and  are  also  frequently 
found  together  in  the  pneumonias  that  complicate  influenza. 
The  results  obtained  in  cases  of  influenza  early  in  the 
disease  before  the  development  of  either  a  purulent  bron- 
chitis or  of  pneumonia  are  presented.  The  presence  of 
pneumococcus  was  determined  by  the  intraperitoneal  inocu- 
lation of  white  mice  with  the  saliva  or  sputum. 

Twenty-four  cases  examined  on  September  27  and  28 
gave  the  results  shown  in  Table  IV.  These  patients  had 
been  in  the  hospital  from  two  to  five  days  at  the  time  the 
determinations  were  made. 


PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATOR?  TRACT 


T.Uil.r    IV 
PNEUMOCOCCUS   ix    Casts  OF    [NFLUENZA 


Pneumococcus^  Type  I 
Pneumococcus,  Type  II 
Pneumococcus,  Atypical   1 1 

Piunimoeoccus,  Typi-  I  !  I 
Pneumococcus,  Group  I  V 
No  pneumococci  found 


NUMBER 

PER    CENT 

0 

0 

0 

0 

0 

0 

0 

8.3 

15 

62.5 

7 

29.2 

From  November  27  to  December  1,  the  pneumococci  pres- 
ent in  47  consecutive  eases  of  influenza  were  determined. 
In  this  group  specimens  of  sputum  were  collected  shortly 
after  admission  of  the  patients  to  the  receiving  ward  of  the 
hospital.     The  results  are  shown  in  Table  V. 


Table  V 
Pneumococci  in  Cases  of  Influenza 


Pneumococcus,  Type  I 
Pneumococcus,  Type  II 
Pneumococcus,  Atypical  II 
Pneumococcus,  Type  III 
Pneumococcus,  Group  IV 
Mo  pneumococci  found. 


PER    CENT 


0 
0 

4.3 

0 
53.2 
42.5 


The  results  obtained  show  that  pneumococci  found  in 
early  uncomplicated  cases  of  influenza,  both  early  and  late 
in  the  course  of  the  epidemic,  differ  in  no  respect  from 
those  found  in  the  mouths  of  normal  individuals  at  any 
time. 

Similar  studies  of  the  prevalence  of  S.  hemolyticus  as 
determined  by  throat  cultures  in  early  cases  of  influenza 
are  shown  in  Table  VI. 

The  only  point  of  interest  in  these  observations  is  the  in- 
creased prevalence  of  S.  hemolyticus  in  cases  examined  late 
in  the  epidemic  of  influenza  as  compared  with  that  found 
early  in  the  epidemic.  The  significance  of  this  will  be  dis- 
cussed in  other  parts  of  this  report. 

Presence  of  Bacillus  Influenzae  in  Normal  Men. — For 
comparison  with  the  results  obtained  in  cases  of  influenza 


ETIOLOGY  OF  INKI/UKXZA  DO 

Table  VI 
S.  Hemolyticus  in  Cases  of  Influenza 


NUMBER   OF  S.    IIEMOLYTI- 

CASES   CULTURED        CUS    FOUND 


S.    HEMOLYTI-    PER    CENT    POSI- 
CUS    NOT  TIVE   FOR   S. 

FOUND  HEMOLYTICUS 


Sept.  25-26         100  6  94  6 

Nov.  27— Dec.  5     138         39  99  28.3 

a  fairly  extensive  study  of  the  prevalence  of  B.  influenzae 
in  normal  individuals  lias  been  made  at  various  times  prior 
to  and  throughout  the  course  of  the  epidemic.  This  was 
deemed  of  special  importance,  since  it  was  obvious  that  the 
results  obtained  by  previous  workers  during  interepidemic 
periods  would  not  in  all  probability  coincide  with  those  ob- 
tained in  the  presence  of  a  widespread  epidemic  of  influ- 
enza where  the  opportunity  for  the  dissemination  of  B.  in- 
fluenzae was  almost  unlimited. 

From  the  results  obtained  in  the  multiple  cultures  in 
cases  of  influenza  it  is  obvious  that  only  like  methods  can 
be  compared.  The  results  obtained  in  normal  individuals 
have,  therefore,  been  tabulated  in  groups  dependent  upon 
the  culture  method  employed.  These  groups  have  been 
subdivided  according  to  the  time  and  the  place  of  the  study, 
such  explanatory  notes  as  seem  necessary  being  added. 
(See  Tables  VII-IX.) 

The  most  striking  feature  of  the  figures  presented  in 
Table  VII  is  the  wide  variation  in  the  incidence  of  B.  influ- 
enzae in  different  groups  varying  all  the  way  from  11.1  to 
68  per  cent.  Analysis  of  these  differences  brings  out  cer- 
tain points  of  great  interest.  It  is  apparent  that  the  per- 
centage of  cases  carrying  B.  influenzae  depended  in  large 
part  upon  the  prevalence  of  respiratory  diseases  in  the 
group  from  which  the  data  were  obtained.  In  the  studies 
made  at  Camp  Funs  ton  prior  to  the  fall  outbreak  of  influ- 
enza in  epidemic  proportions,  it  is  noteworthy  that  "bron- 
chitis ' '  and  pneumonia  were  prevalent  throughout  the  sum- 
mer in  those  groups  showing  a  relatively  high  incidence  of 
B.  influenzae.    At  the  time  these  studies  were  made  the  pres- 


.ill 


PNEUMONIAS  AND    INFECTIONS  OF   R 


'IRATORY  TRACT 


Tabli    VII 

Incidence  of   B.    Influenzae  ix   Normal    Men    as    Determined   \-\    INTRA- 
PERITONEAL    l\oi  Tl.\TiON    OF    WHITE     MlCE    \\  III  I    SALIVA    OR    SPUTUM 


a 

v. 

o 

r- 
N 
V. 

O 

- 

- 

a   g 

H    - 
n    ^ 

~    -*, 

g    X 

v.  M 

■a 

X 

V. 

-  g 
g    X 

I  - 

-  c 

.     & 
03 

PER    CENT 
POSITIVE    FOR 
li.  INFLUENZAE 

REM  VRKS 

1918 

Aug. 

13 

i  lamp 

Funston,      22  Prov. 
K.-uis.  De-    Colored 
bention         Co.  104th 
Camp,          Depot 
No.  2            Brigade 

25 

6 

21 

Bronchitis  and  pneumonia 
were  prevalenl  in  this  or- 
ganization    of     r  e  c  e  n  t  1  y 

d  i.-i  £ted  aegroes  'luring  July 
and  August,   15)18 

Aug. 
18 

Camp           Co.  D.  3rd 
Punston,      Dev.  Bn. 

Kims.  De- 
tention 
<  lamp, 
No.  2 

25 

11 

44 

Recently  drafted  southern 
negroes  not  fit  for  full  mili- 
tary duty.  Bronchitis  and 
pneumonia  were  prevalent 
in  this  organization  during 
July  and  August,  1918 

Aug. 
20 

Camp 

Funston, 
Kan. 

70th  Inf. 

25 

11 

44 

25  men  presenting  them- 
selves at  sick  call  for  vari- 
ous complaints;  not  Btrict- 
ly  normal;  respiratory  dis- 
eases not  prevalenl 

Aug. 
22 

Ft.  Riley 
Kan. 

Quarters 

4M 

M.O.T.C. 

32 

16 

50 

Recently  drafted  white   men 
of  4  to  8  weeks'  service. 
Pneumonia   fairly  prevalent 
in  this  organization 

Aug. 
26 

Camp 

Funston, 

Kan. 

210th  Eng. 

27 

3 

11.1 

About  one  mile  distant  from 
Camp  Funston  proper.  No 
sickness  in  this  organiza- 
tion 

Nov. 
12 

Hot 
Springs, 

Ark. 

Drafted 
men 

assembled 
to  ''tit  rain 
for  camp 

50 

11 
13 

22 

50  men  selected  from  iso- 
lated farm  communities;  12 
gave  a  history  of  "influen- 
za" within  the  preceding  8 

Weeks 

Nov. 
25 

Camp  Pike 
Ark. 

Miscella- 
neous 

26 

50 

12  of  this  group  had  influ- 
enza   during  the  epidemic 

Dec. 
10 

Camp  Pike 
Ark. 

Miscella- 
neous 

25 

17 

68 

12  of  this  group  had  influ- 
enza during  the  epidemic 

Summary: 

Normals 

Cases  of 
influenza 
(for  com- 
parison) 

235 
76 

88 
61 

37.4 
80.3 

ETIOLOGY  OF  INFLUENZA  37 

ence  of  influenza  in  these  organizations  was  not  recognized, 
but  in  view  of  knowledge  gained  throng}) out  the  course  of 
the  epidemic  at  Camp  Pike,  it  seems  not  improbable  that 
influenza  in  mild  form  was  present  throughout  the  summer 
in  certain  organizations  at  Camp  Funston.  This  would 
seem  more  likely  in  view  of  the  fact  that  this  commission 
has  clearly  demonstrated  that  a  considerable  epidemic  of 
influenza  swept  through  Camp  Funston  in  March,  1918,  and 
was  followed  by  recurring  smaller  epidemics  in  April  and 
May.14  In  contrast  with  these  groups  showing  a  high  inci- 
dence of  B.  influenza)  is  that  of  the  210th  Engineers,  an  or- 
ganization entirely  free  from  respiratory  diseases  during 
the  period  of  our  study. 

On  November  12  search  was  made  for  Bi.  influenzae  in  50 
normal  drafted  men  who  had  assembled  at  Hot  Springs, 
Ark.,  on  that  date  preparatory  to  entraining  for  Camp 
Pike.  These  men  were  all  from  isolated  farming  communi- 
ties where  influenza  was  only  moderately  prevalent  and 
where  there  was  little  opportunity  for  the  wide  dissemina- 
tion of  B.  influenzae  such  as  occurs  when  large  bodies  of 
men  are  assembled  in  camps.  Twelve  of  the  50  gave  a  his- 
tory of  influenza  within  the  preceding  eight  weeks.  The 
cultures  were  made  by  the  same  methods  as  those  used  at 
Camp  Pike,  the  laboratory  car  "Lister"  being  taken  to 
Hot  Springs  for  that  purpose.  The  incidence  of  B.  influ- 
enzae was  only  22  per  cent.  In  striking  contrast  with  this 
figure  are  the  figures  of  50  and  68  per  cent  obtained  in  the 
last  two  groups  studied  at  Camp  Pike  after  the  epidemic 
had  swept  through  the  camp:  24  of  the  51  men  in  these 
groups  had  influenza  during  the  epidemic. 

It  is  of  interest  to  record  that  the  incidence  of  pneumo- 
coccus  in  these  cases  was  approximately  the  same  in  all 
groups  and  bore  no  relation  to  the  prevalence  of  influenza, 
bronchitis,  or  pneumonia. 

140pie,    Freeman,    Blake,    Small,   and   Rivers:     Jour.   Am.    Med.    Assn.,    1919,    lxxii,    108. 


•>  a 


PNEUMONIAS  AND   INFECTIONS  OF   RESPIRATORS  TRACT 


Table  VII] 

Incidence  of   r>.   [npluenz2e  in    Normal   Men    as   Determined  ky   Throat 

1      1  n  ki:s  ox   Hi.ook  A<;ak  Plates 


< 

c 
< 
- 

- 

ts; 

h 

0  S 

a 

-  _ 
?•  < 

-    X 

3 

s: 
V. 

§  1! 

SB 

g    Efl 

.    M 

23    C- 

PEB  CENT 
POSITIVE    FOR 
B.   INFLUENZAE 

REMARKS 

Sept. 
Oct.  5 

Camp 
Pike, 

Ark. 

Med.  De-             82 
tachment, 
Base  11  os. ; 
personnel 

on  measles 

wanls 

14 

17.1 

82  throat  cultures  in  42 
individuals 

Nov. 
5-9 

Camp 

Pike 

Ark. 

Miscella-           296 
neous 

71 

23.9 

Number  among  this  group 
who  had  had  influenza 
no!   recorded 

Nov.  12 

Hot 

Springs, 
Ark. 

Drafted               64 
men  assem- 
bled  to  en- 
train for 
camp 

0 

0 

Mi 'ii,  in  large  part  from 
isolated  farm  communi- 
ties; 13  gave  a  history 
of  "influenza"  within 
the    preceding    8    weeks 

Nov.  25 

Camp 
Pike 

Miscella-             26 
neous 

13 

50 

12  of  this  group  had  in- 
fluenza during  the  epi- 
demic 

Dee.  10 

Camp 
Pike 

Miscella- 
neous 

25 

13 

52 

12  of  this  group  had  influ- 
enza, during  the  epidemic 

Summary 

Normals           493 
Cases  of  in- 
fluenza   (for 
comparison);   166 

111 

109 

22.5 
65.7 

The  results  obtained  by  throat  culture  are  quite  similar 
to  those  obtained  by  the  mouse  inoculation  method.  The 
entire  absence  of  B.  influenzae  in  the  group  of  64  throat  cul- 
tures made  in  the  draft  men  assembled  at  Hot  Springs  as 
compared  with  the  relatively  high  incidence  in  the  last  two 
groups  examined  at  Camp  Pike  is  very  striking. 

In  consideration  of  the  figures  presented  in  Table  IX 
it  is  important  to  remember  that  the  group  of  50  men  from 
Hot  Springs  were  all  from  isolated  farm  communities,  had 
not  previously  been  assembled  and  had  not  been  in  continu- 
ous contact  with  a  widespread  epidemic  of  influenza.  On 
the  other  hand,  the  two  groups  of  normal  men  at  Camp 
Pike   were   studied   immediately   after   the   epidemic   had 


ETIOLOGY  OK    IXKLUKX/A 


39 


Table  IX 

Incidence  op  B.   Influenza  in   Normal    Men  Contrasted  With  That  in 

Early  Cases  op  Influenza  as  Determined  by  Multiple  Cultures 

from  Nose,  Throat,  and  Sputum 


o 

P 

o 

O 

a 

H 

W    £ 
M    5 

P    W 

PER 

CENT    SHOWING    B.    INFLUENZA 

a 

w 
o 

"A 

o 

K 

SPUTUM 

DIRECT 

CULTURE 

SPUTUM 

MOUSE 

INOCULATION 

w 
3 

a- 

^  w 

r  « 
£  P 

05    U 

Nov. 

Hot 

Normal 

50 

0 

0 

0 

22 

22 

12 

Springs, 

draft    men 

(4  cul- 
tures 
only) 

(31 

Ark. 

assembled 

cul- 

to entrain 

tures 

for  camp 

only) 

Nov. 

Camp  Pike 

Normal 

26 

38.6 

50 

34.6 

50 

80.8 

25 

men;   12 
had  influ- 
enza dur- 
ing the  epi- 
demic 

Dec. 

Camp  Pike 

Normal 

25 

48 

52 

24 

68 

88 

10 

men ;   12 
had   influ- 
enza dur- 
ing the  epi- 
demic 

Oct, 

Camp  Pike 

Patients 

28 

21.4 

50 

60.7 

78.6 

100 

10 

with   influ- 

and 

enza  in 

' 

Nov. 

Base  Hos. 

19 

•swept  through  the  camp  and  had  been  constantly  in  contact 
with  epidemic  influenza  for  a  period  of  three  months,  24  of 
the  51  actually  having  had  the  disease  during  this  period. 
The  fact  that  in  the  group  of  men  from  Hot  Springs,  B. 
influenzae  was  found  only  by  the  mouse  inoculation  method 
is  noteworthy,  since  it  indicates  that  the  organism  was  pres- 
ent in  relatively  small  numbers  and  could  be  detected  only 
by  a  highly  selective  method. 

Summary  of  the  results  obtained  in  normal  men  shows 
that  the  incidence  of  B.  influenzae  in  normal  individuals 
from  isolated  communities  or  in  groups  free  from  respira- 
tory diseases  prior  to  the  occurrence  of  the  fall  epidemic 


40 


PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATORY  TRACT 


was  relatively  low,  namely,  10  to  20  per  cent;  that  in  ob- 
servations made  before  the  fall  epidemic  in  groups  in  which 
"bronchitis"  and  pneumonia  were  fairly  prevalent,  B.  in- 
fluenzae was  found  much  more  frequently,  namely,  in  25  to 
50  per  cent  of  the  cases;  and  thai  in  groups  studied  at  in- 
tervals during  the  epidemic  the  incidence  of  B.  influenzae 
rapidly  rose,  peaching  85  per  cent  at  the  end  of  the  epi- 
demic. In  contrast  with  this.  B.  influenzae  was  found  in  100 
per  cent  of  cases  of  influenza  without  reference  to  the  time 
at  which  they  occurred  during  the  epidemic.  It  is  obvious 
that  the  high  percentage  of  normal  men  carrying  B.  influ- 
enzae found  at  the  end  of  the  epidemic  can  depend  only  on 
the  wide  dissemination  of  B.  influenzae  that  must  occur  dur- 
ing epidemic  times. 

Bacillus  Influenzas  in  Measles. — Since  the  presence  of  B. 
influenzae  in  other  diseases  than  influenza  has  been  ad- 
vanced as  an  argument  against  its  causal  relationship  to 
influenza,  an  extensive  study  of  the  incidence  of  B.  influenzae 
in  the  throats  of  measles  patients  was  made  during  the  pe- 
riod of  the  epidemic  of  influenza  at  Camp  Pike  from  Sep- 
tember 10  to  October  20.  In  all  a  total  of  830  throat  cul- 
tures in  487  cases  of  measles  were  made,  many  cases  being 
cultured  repeatedly  at  weekly  intervals.  The  results  have 
been  condensed  as  far  as  possible  and  are  presented  in 
Tables  X,  XI,  XII. 

Table  X 

Incidence  of  B.  Influenzae  in   400  Consecutive  Casks  of  Measles  as  De- 
termined by  Throat  Culture  at  Time  of  Admission  to  the  Base 

Hosimtal 


DATE 

NUMBER    OF 

CASES 

B.    INFLUENZAE    FOUND 

NUMBER 

PEB   CENT 

Sept.    16— Oct.   4 
Oct.  4— Oct.  10 
Oct.   10— Oct.   15 
Oct.   15— Oct.   19 

100 

nm 

100 
100 

27 

32 

32 
48 

27 
32 

32 
48 

The  prevalence  of  B.  influenza'  in  cases  of  measles  during 
the  period  of  the  influenza  epidemic  corresponded  very 
closelv  with  that  found  in  normal  individuals  under  similar 


ETIOLOGY  OK    INKU'KNXA 


41 


Table  XI 

Incidence  of  B.  Influenza  in  830  Throat  Cultures  in  487  Cases  of  Mea- 
sles;  Cultures  Eepeated  at  Weekly  Intervals 


NUMBER    OF 

CULTURES 

B.    INFLUENZAE    FOUND 

NUMBER 

PER  CENT 

Sept.  10-15 
Sept.   16-29 
Sept.  30— Oct.  6 
Oct.  7-13 
Oct.  14-20 

47 

106 
122 
235 
320 

15 

33 

38 

96 

157 

31.9 
31.1 

31.1 

40.8 
49.1 

Total 

830 

339 

40.8 

circumstances.  The  increasing  proportion  of  cases  carry- 
ing B.  influenzae  as  the  epidemic  of  influenza  advanced  is 
further  evidence  of  the  wide  dissemination  of  the  organism 
during  the  epidemic. 

Table  XII 

Total  Number  of  B.  Influenza  Carriers  Among   223    Cases    of   Measles 

as  Determined  by  Repeated  Throat  Cultures  at  Weekly 

Intervals  after  Admission  to  Hospital 


TOTAL    CARRIERS   IN 

times 

NUMBER 

NUMBER 

B.   INFLUENZA  FOUND 

ONE   OR   MORE 

CULTURED 

OF  CASES 

OF 
CULTURES 

CULTURES 

NUMBER 

PER  CENT 

NUMBER 

PER  CENT 

2 

129 

1st 
2nd 

37 

63 

28.7 

48.8 

82 

63.6 

3 

69 

1st 
2nd 
3rd 

20 
31 
33 

28.9 
44.9 

47.8 

52 

75.4 

4 

25 

1st 
2nd 
3rd 
4th 

6 
10 
13 
14 

24 
40 
52 
56 

21 

84.0 

It  is  evident  from  the  figures  presented  in  Table  XII  that 
a  large  percentage  of  the  measles  cases  studied  were  at  one 
time  or  another  carriers  of  B.  influenza?.  In  consideration 
of  this  fact,  it  must  be  borne  in  mind  that  all  these  cases 
were  cultured  during  the  period  when  the  influenza  epi- 
demic was  at  its  height  and  that  many  of  these  cases  had  in- 
fluenza while  in  the  hospital  for  measles.  Xo  data  are 
available  as  to  the  exact  number,  since  a  definite  diagnosis 
of  influenza  could  hardly  be  made  during  the  acute  stage  of 
measles.     It  is  probable  that  approximately  25  per  cent 


4'2        PNEUMONIAS  AND  [NFECTIONS  OF  RESPIRATOR?  TRACT 

developed  influenza,  since  that  was  the  incidence  of  influ- 
enza in  the  total  population  of  Camp  Pike.  The  consistent 
increase  in  the  percentage  of  influenza  carriers  clearly 
demonstrates  that  this  was  due  to  wide  dissemination  of 
B.  influenzae  with  the  progress  of  the  epidemic.  Another 
point  of  exceeding  interest  is  that  the  percentage  of  meas- 
les cases  carrying-  B.  influenzae  in  the  throat  was  lowest  dur- 
ing the  acute  stage  of  the  disease  and  increased  during  con- 
valescence. This  is  in  direct  contrast  with  the  results  found 
in  cases  of  influenza  where  the  number  of  cases  carrying  B. 
influenzae  in  the  throat  Avas  highest  during  the  acute  -stage 
and  rapidly  diminished  in  uncomplicated  cases  with  the  on- 
set of  convalescence. 

Summary. — Multiple  cultures  made  simultaneously  from 
the  nose,  throat  and  lower  respiratory  tract  showed  that 
B.  influenzae  was  invariably  present  in  all  cases  of  influenza 
from  the  onset  of  the  disease.  Not  only  was  B.  influenzae 
present  in  all  cases,  hut  it  was  frequently  present  in  pre- 
dominant numbers,  sometimes  in  nearly  pure  culture.  In 
the  majority  of  cases  that  went  on  to  rapid  recovery  with- 
out the  development  of  an  extensive  bronchitis  or  compli- 
cating pneumonia,  the  predominance  of  B.  influenzae  over 
other  organisms  rapidly  diminished  coincident  with  onset 
of  convalescence.  Many  cases,  however,  continued  to  carry 
B.  influenza?  in  large  numbers  in  the  throat  throughout  con- 
valescence. Xo  data  on  the  possible  duration  of  the  carrier 
state  have  been  obtained.  By  the  culture  methods  em- 
ployed no  other  organism  has  been  found  that  would  sug- 
gest any  etiologic  relationship  to  the  disease.  The  two 
organisms  most  frequently  associated  with  B.  influenzae  in 
postinfluenzal  pneumonias,  pneumococcus  and  S.  hemolyti- 
cus,  have  not  differed  in  their  incidence  in  early  uncom- 
plicated cases  of  influenza  from  that  found  in  normal  in- 
dividuals. 

The  incidence  of  B.  influenzae  in  normal  men,  in  different 
groups  studied,  has  varied  between  11.1  and  88  per  cent. 


ETIOLOGY  OF  INFLUENZA  4d 

This  wide  variation  has  depended  npon  the  prevalence  of 
respiratory  diseases,  more  particularly  influenza,  in  the 
groups  studied  and  the  opportunity  thereby  offered  for  the 
wide  dissemination  of  B.  influenza.  With  the  progress  of 
the  epidemic,  the  number  of  normal  men  carrying  B.  in- 
fluenzae has  steadily  increased  until  it  reached  its  maximum 
at  the  end  of  the  epidemic. 

The  incidence  of  B.  influenzae  in  cases  of  measles  studied 
during  the  epidemic  of  influenza  has  been  relatively  high 
though  never  equaling  that  found  in  cases  of  influenza.  As 
in  normal  men,  the  incidence  in  cases  of  measles  has  stead- 
ily increased  during  the  period  of  the  epidemic.  Repeated 
throat  cultures  at  weekly  intervals  in  cases  of  measles  have 
shown  that  approximately  80  per  cent  became  temporary 
carriers  of  B.  influenzae  at  one  time  or  another  during  the 
period  of  the  epidemic.  Many  of  these  cases  had  influenza 
during  the  time  that  they  were  in  the  hospital.  The  carrier 
state  in  cases  of  measles  was  found  to  bear  no  relation  to 
the  acute  stage  of  the  disease  since  the  number  of  carriers 
at  the  time  of  admission  to  the  hospital  was  considerably 
lower  than  that  found  during  convalescence  as  determined 
by  repeated  cultures  in  the  same  cases. 

Discussion 

The  bacteriologic  studies  in  cases  of  influenza  described 
in  this  report  fully  support  Pfeiffer's  claim  that  B.  influ- 
enzae is  invariably  present  in  the  disease.  It  is  particularly 
important  to  note  that  these  results  were  obtained  in  early 
uncomplicated  cases  of  influenza  and  are  not  dependent 
upon  cultures  made  from  cases  complicated  by  pneumonia 
or  obtained  at  autopsy.  In  view  of  this  fact  the  tendency 
so  apparent  in  much  of  the  recent  literature  to  relegate  B. 
influenzae  to  a  place  of  secondary  or  minor  importance  in 
the  disease  seems  hardly  justifiable.  It  would  seem  that 
this  tendency  is  largely  dependent  upon  three  factors :  first, 
the  failure  of  many  to  find  B.  influenza?  either  during  life  or 


44        PNEUMONIAS  AND   INFECTIONS  OF   RESPIRATOR?  TRACT 

a1  autopsy  in  any  considerable  proportion  of  cases;  second, 
the  frequenl  failure  to  draw  a  clear  distinction  between  in- 
fluenza itself  and  the  pneumonia  to  which  it  predisposes 
with  a  consequent  overemphasis  upon  autopsy  bacteriology 
where  a  considerable  variety  of  secondary  organisms  have 
attracted  particular  attention:  and  third,  an  incorrect  in- 
terpretation of  the  undoubtedly  Large  number  of  B.  influ- 
enzae carriers  Pound  among  normal  individuals  and  those 
with  other  diseases  during  the  period  of  the  epidemic  and 
to  less  extent  in  interepideinic  times. 

Since  the  majority  of  workers  who  are  thoroughly  fa- 
miliar with  the  technic  of  cultivating  B.  influenzal  have  en- 
countered little  difficulty  in  finding  it  in  a  large  majority 
of  cases,  it  is  felt  that  the  considerable  number  of  negative 
reports  that  have  appeared  can  depend  only  upon  the  un- 
familiarity  of  those  who  have  failed  to  find  it  with  the 
proper  bacteriologic  methods.  This  is  quite  apparent  in 
many  of  the  reports  that  have  been  published,  and  is  not 
surprising  in  the  face  of  the  excessive  demand  for  well- 
trained  bacteriologists  occasioned  by  the  war. 

One  important  feature  in  the  successful  isolation  of  B. 
influenzae  from  all  cases  that  has  been  brought  out  in  the 
course  of  the  work  here  reported,  is  the  necessity  of  making 
simultaneous  cultures  from  all  portions  of  the  respiratory 
tract,  since  by  no  single  culture  method  was  it  found  possi- 
ble to  find  the  organism  in  all  cases.  It  has  been  pointed 
out  that  one  of  the  most  characteristic  local  phenomena  of 
the  disease  is  the  rapidly  progressing  attack  upon  the  mu- 
cous membranes  of  the  respiratory  tract.  Tt  seems  quite 
possible  that  B.  influenza'  in  predominant  numbers  at  least 
may  be  found  in  many  cases  only  at  the  crest  of  the  wave, 
if  we  may  speak  of  it  as  such.  By  way  of  analogy  is  the 
well-recognized  fad  that  the  successful  isolation  of  strep- 
tococcus from  eases  of  erysipelas  often  depends  upon  tak- 
ing cultures  from  the  margin  of  the  advancing  lesion.  While 
definite  proof  is  lacking  for  this  opinion,  it  would  seem  to 


ETIOLOGY   OF    IXKIJ'KX/A  45 

receive  some  support  from  the  observation  that  15.  influ- 
enzae rapidly  disappears  from  the  throat  with  the  onset  of 
convalescence  in  a  considerable  proportion  of  eases.  It  is 
felt  that  these  observations,  establishing  the  predominance 
of  B.  influenzae  in  the  early  acute  stages  of  the  disease,  are 
of  considerable  significance,  especially  when  exactly  the  re- 
verse condition  was  found  in  studying  the  incidence  of  the 
organism  in  cases  of  measles. 

In  consideration  of  the  primary  cause  of  influenza,  atten- 
tion has  often  been  focused  upon  the  many  different  bacteria 
found  in  autopsy  cultures.  The  most  prominent  of  these 
are  the  ill-defined  cliplostreptococci  of  the  European  writ- 
ers, the  various  immunologic  types  of  pneumococci,  and  S. 
hemolyticus.  Other  microorganisms  less  frequently  found 
are  staphylococci,  M.  catarrhalis,  nonhemolytic  strepto- 
cocci, and  B.  mucosus  capsulatus.  It  is  not  within  the  scope 
of  this  paper  to  discuss  their  relation  to  the  various  types 
of  pneumonia  found  at  autopsy,  but  their  very  multiplicity 
would  seem  sufficient  prima  facie  evidence  that  they  bear 
no  etiologic  relationship  to  influenza  and  must  be  regarded 
only  as  secondary  invaders.  If  any  further  support  for  this 
opinion  were  necessary,  it  may  be  found  in  the  studies  upon 
the  incidence  of  pneumococcus  and  S.  hemolyticus  in  early 
cases  of  influenza  described  in  this  report.  Both  were  found 
to  occur  in  the  same  proportions  in  which  they  may  be 
found  in  normal  individuals  at  any  time. 

Although  Pfeiffer  maintained  that  B.  influenzae  was 
found  only  in  true  epidemic  influenza,  the  incorrectness  of 
this  contention  has  been  thoroughly  established  by  many 
reliable  investigators  and  it  has  been  shown  beyond  ques- 
tion that  influenza  bacilli  may  always  be  found  in  a  small 
proportion  of  normal  individuals  and  are  not  infrequently 
found  in  other  respiratory  diseases. 

The  fairly  extensive  study  that  has  been  made  of  the  in- 
cidence of  B.  influenzae  in  normal  men  and  in  cases  of  mea- 
sles has  clearly  demonstrated  that  the  proportion  of  car- 


4l!        PNEUMONIAS  AND   [NFECTIONS  OF  RESPIRATOR'S  TRACT 

riers  found  in  any  group  depends  upon  the  prevalence  of 
influenza  in  the  group  studied  and  thai  with  the  progress 
of  the  epidemic  the  percentage  of  carriers  has  steadily  in- 
creased. When  one  considers  that  the  opportunity  i'or  the 
dissemination  of  B.  influenzae  by  contact  infection  is  almost 
unlimited  during  an  epidemic  of  the  proportions  of  that 
which  has  swept  over  the  country,  this  is  not  at  all  surpris- 
ing. That  such  a  large  number  of  normal  individuals  be- 
came carriers  of  B.  influenzae  during  the  epidemic  would 
seem  to  be  sufficient  evidence  that  actual  dissemination  does 
occur  and  to  controvert  the  theory  that  in  actual  cases  of 
influenza,  conditions  are  established  in  the  respiratory  tract 
whereby  B.  influenzas,  always  present  in  small  numbers,  is 
enabled  to  "grow  out"  and  become  the  predominant  or- 
ganism. From  a  consideration  of  all  the  observations  made 
as  to  the  incidence  of  B.  influenzae  in  various  conditions  it 
would  appear  that  the  carrier  condition  is  quite  analogous 
to  that  found  with  many  other  bacteria,  and  may  be  divided 
into  three  groups:  (a)  acute  carriers,  those  having  influ- 
enza, (b)  contact  carriers,  those  who  during  epidemic  times 
become  temporary  carriers  of  the  organism  without  con- 
tracting the  disease,  and  (c)  chronic  carriers,  the  relatively 
small  number  of  normal  individuals  or  those  with  chronic 
respiratory  conditions  who  carry  B.  influenzae  over  long 
periods  of  time.  From  the  facts  at  hand  this  would  seem  to 
be  the  most  probable  explanation  of  the  conditions  found. 
It  is  certainly  true  that  the  established  presence  of  pneu- 
mococcus,  B.  diphtheria?,  meningococcus  and  many  other 
organisms  in  a  varying  proportion  of  normal  individuals  is 
not  regarded  as  sufficient  evidence  to  exclude  them  as  the 
etiologic  agents  of  the  diseases  which  they  cause. 

It  is  quite  obvious  that  if  B.  influenzae  is  to  be  regarded 
as  the  cause  of  epidemic  influenza,  it  must  change  quite 
rapidly  under  certain  circumstances  from  a  relatively  sap- 
rophytic organism  to  a  relatively  virulent  pathogenic  or- 
ganism, and  conversely  return  to  its  avirulent  state  follow- 


ETIOLOGY  OF    I  X  KM  'K  X/A  47 

ing  the  passage  of  an  epidemic  Animal  experimentation 
has  taught  us  that  virulence  is  acquired  by  the,  rapid  pas- 
sage of  an  organism  'from  host  to  host.  That  an  oppor- 
tunity for  the  rapid  transference  of  B.  influenza?  from  man 
to  man  was  provided  by  the  assembling  of  large  groups  of 
individuals  relatively  susceptible  to  respiratory  diseases 
in  our  camps  and  cantonments  is  by  no  means  impossible. 
It  has  been  clearly  shown  by  Vaughn  and  Palmer15  that 
men  from  rural  districts  are  very  susceptible  to  respiratory 
diseases  and  that  the  camps  in  which  such  men  were  as- 
sembled suffered  most  heavily  in  this  respect  during  the 
winter  of  1917-18.  This  Commission  has  clearly  demon- 
strated that  an  epidemic  of  influenza  swept  through  Camp 
Funston14  in  the  spring  of  1918  and  that  a  similar  epidemic 
occurred  at  Camp  Pike.  Accumulating  evidence  will  un- 
doubtedly show  that  like  epidemics  existed  in  many  of  our 
southern  camps  (Vaughn  and  Palmer,15  Soper16).  It  is  of 
considerable  interest  that  B.  influenzae  was  found  in  almost 
one-half  of  the  cases  of  bronchopneumonia  'studied  by  Cole 
and  MacCallum17  at  Fort  Sam  Houston  in  February  and 
March,  1918.  This  relation  is  especially  noteworthy,  since 
an  epidemic  of  influenza  was  seen  by  one  of  us  (Blake) 
among  the  troops  at  Kelly  Field  and  Fort  Sam  Houston 
during  these  months.  That  similar  conditions  existed  in 
European  armies  as  early  as  1916-17  is  suggested  by  the 
reports  of  Hammond,  Eolland,  and.  Shore18  and  of  Abra- 
hams, Hallows,  Eyre,  and  French19  on  epidemics  of  "pur- 
ulent bronchitis"  with  bronchopneumonia  in  the  British 
army.    B.  influenzae  was  found  abundantly  in  these  cases. 

Theoretically,  under  the  conditions  outlined,  above,  ideal 
opportunities  have  been  provided  for  B.  influenzae  to  build 
up  sufficient  virulence  to  enable  it  to  produce  the  pandemic 
of  1918-19.     While  it  is  thoroughly  recognized  that  these 

15Vaughn  and  Palmer:     Jour.   Lab.  and  Clin.   Med.,   1918,   iii,   635. 
16Soper:     Jour.   Am.    Med.   Assn.,    1918,   bcxi,    1899. 
1TCole  and  MacCallum:     Jour.   Am.    Med.  Assn.,    1918,   lxx,    1146. 
"Hammond,    Rolland,    and    Shore:      Lancet,    London,    1917,    ii,    41. 
10Abrahams,   Hallows,    Eyre,   and    French:     Lancet,    London,    1917,    ii,    377. 


4-S         PNEUMONIAS  AND   INFECTIONS  OF   RESPIRATORS  TRACT 

considerations  are  in  the  main  hypothetical,  it  is  felt  that 
they  are  by  bo  means  beyond  the  bounds  of  possibility,  and 
for  thai  reason  arc  offered  as  suggestions  worthy  of  l'ur- 
i her  investigation. 

It  is,  of  course,  perfectly  possible  on  the  basis  of  the  ob- 
servations presented  still  to  regard  B.  influenzae  as  a  sec- 
ondary invader  which  makes  its  appearance  in  all  cases  of 
influenza  simultaneously  with  the  onset  of  clinical  symp- 
toms. Final  proof  of  its  causal  relationship  to  the  disease 
must  depend  upon  the  production  of  influenza  by  experi- 
mental inoculation.  Results  hitherto  obtained  in  attempts 
to  produce  the  disease  experimentally  have  been  contra- 
dictory. ri'eifl'er1  claimed  to  have  produced  a  disease  in 
monkeys  in  some  respects  resembling  influenza  by  the  in- 
tratracheal injection  of  freshly  isolated  cultures  of  B.  in- 
fluenzae. Wollstein,12  in  studies  upon  the  pathogenicity  of 
various  strains,  has  shown  that  B.  influenzae  is  generally 
pathogenic  for  mice  and  guinea-pigs  without  respect  to 
source  or  virulence  for  man.  Pathogenicity  for  rabbits 
and  monkeys,  on  the  other  hand,  was  possessed  only  by 
strains  that  were  highly  virulent  for  man.  She  further- 
more pointed  out  that  for  successful  animal  experimenta- 
tion, it  is  imperative  that  inoculations  be  carried  out  im- 
mediately after  the  isolation  of  the  bacilli  because  they  rap- 
idly lose  virulence  by  subculture  on  artificial  media.  It  is 
felt  that  failure  to  appreciate  these  facts  has  been  respon- 
sible for  the  often  repeated  statement  that  B.  influenzae  is 
not  pathogenic  for  animals. 

In  a  series  of  animal  experiments  carried  out  by  this  com- 
mission recorded  in  an  appendix  to  this  report,  sixteen- 
hour  cultures  of  B.  influenzae  freshly  isolated  from  early 
cases  of  influenza  were  demonstrated  to  be  pathogenic  for 
monkeys,  both  by  inoculation  of  the  nasal  and  pharyngeal 
mucosa  and  by  intratracheal  injection.  Monkeys  so  inocu- 
lated developed  coryza,  epistaxis,  tracheitis,  bronchitis,  and 
extreme  prostration.     Experiments  with  forty-eight-hour 


ETIOLOGY  OF   I  NK'LUUXZA  41) 

cultures  of  strains  preserved  by  subculture  during  from  ten 
to  fifteen  days  failed  to  demonstrate  pathogenicity  for  mon- 
keys. Proof  that  these  monkeys  had  influenza  can  depend 
only  upon  the  demonstration  that  they  suffered  with  a  dis- 
ease having  the  clinical  character  and  pathologic  lesions  of 
influenza. 

The  reported  failure  to  produce  influenza  in  man  by  di- 
rect inoculation  with  freshly  isolated  cultures  of  B.  influ- 
enzae in  experiments  conducted  on  volunteers  by  the  United 
States  Public  Health  Service20  at  Gallops  Island,  Boston, 
is  interesting,  but  would  seem  to  lack  definite  significance 
since  attempts  to  transmit  the  disease  from  man  to  man  by 
direct  contact  also  failed.  Since  all  the  subjects  of  these 
experiments  had  been  previously  exposed  to  influenza  dur- 
ing the  epidemic,  30  per  cent  actually  having  contracted  the 
disease,  it  would  seem  probable  that  the  remaining  70  per 
cent  were  only  very  slightly  if  at  all  susceptible.  It  is  note- 
worthy that  the  attack  rate  of  influenza  in  most  army 
groups  was  approximately  20  to  30  per  cent  during  the  epi- 
demic, the  remaining  70  to  80  per  cent  failing  to  contract 
the  disease  though  equally  exposed.  No  other  explanation 
presents  itself  except  that  influenza  is  no  longer  transmis- 
sible when  clinical  symptoms  have  appeared. 

Conclusions 

1.  Consideration  of  all  the  evidence  available  makes  it 
seem  highly  probable  that  B.  influenzae  is  the  specific  etio- 
logic  agent  of  epidemic  influenza,  because  (a)  it  is  always 
present  in  early  uncomplicated  cases  of  influenza;  (b)  it  is 
predominantly  so  during  the  acute  stage  of  the  disease  in 
cases  going  on  to  rapid  recovery  without  development  of 
complications;  (c)  its  presence  in  varying  numbers  in  nor- 
mal individuals  and  in  other  diseases  of  the  respiratory 
tract  is  not  valid  evidence  against  its  etiologic  relationship 
to  influenza,  but  on  the  contrary  is  quite  in  harmony  with 

""Public   Health   Reports,   U.S.P.H.    Service,    1919,   xxxiv,    33. 


50        PNEUMONIAS  AND  INFECTIONS  OF  RESPIRATORY  TRACT 

what  should  be  expected  from  our  knowledge  of  oilier  bac- 
teria known  to  be  the  etiologie  agents  of  various  respira- 
tory diseases;  (d)  its  vapidly  increasing  prevalence  in  nor- 
mal individuals  simultaneously  with  the  progress  of  the 

epidemic  indicates  that  actual  dissemination  of  B.  influenzae 
readily  occurs  and  is  very  widespread  during  pandemic 
times;  (e)  cultures  of  B.  influenzas  freshly  isolated  from 
early  acute  cases  of  influenza  are  pathogenic  for  animals, 
and  may  produce  in  monkeys  a  disease  closely  resembling 
influenza. 

2.  Final  proof  of  the  exact  relationship  of  B.  influenzae 
to  influenza  must  depend  upon  (a)  more  definite  knowledge 
of  the  immunology  both  of  the  organism  and  of  the  disease, 
and  (b)  knowledge  of  the  pathologic  lesions  of  influenza 
and  the  production  of  these  lesions  in  animals  by  inocula- 
tion with  B.  influenzae. 


CHAPTER  II 

CLINICAL  FEATURES  AND  BACTERIOLOGY  OF  IN- 
FLUENZA AND  ITS  ASSOCIATED  PURULENT 
BRONCHITIS  AND  PNEUMONIA 

Francis  G.  Blake,  M.D.,  and  Thomas  M.  Rivers,  M.D. 

The  material  presented  in  this  section  of  the  report  con- 
sists of  clinical  and  bacteriologic  observations  made  dur- 
ing the  course  of  an  investigation  of  influenza  and  its  asso- 
ciated bronchitis  and  pneumonia  at  Camp  Pike,  Ark.,  be- 
tween September  6  and  December  15,  1918,  comprising  part 
of  a  correlated  study  of  the  epidemiology,  bacteriology, 
pathology,  and  clinical  features  of  these  diseases.  The  bac- 
teriologic studies  are  in  the  main  limited  to  those  made  dur- 
ing life,  those  made  at  necropsy  being  reported  in  another 
section  of  this  report. 

Methods. — All  cases  upon  which  the  clinical  and  bacte- 
riologic data  presented  are  based,  were  examined  by  the 
authors  and  our  own  clinical  histories  and  physical  exam- 
inations were  recorded.  This  was  considered  of  special  im- 
portance, since  in  studying  a  group  of  diseases  in  which 
secondary  infection  of  the  respiratory  tract  might  super- 
vene at  any  time,  it  was  essential  to  determine  as  far  as 
possible  the  exact  clinical  condition  of  the  patient  at  the 
time  when  bacteriologic  examinations  were  made.  The  bac- 
teriologic methods  employed  were  the  direct  culture  of 
nose  and  throat  swabbings  and  of  selected  and  washed 
specimens  of  sputum  on  the  surface  of  5  per  cent  defibri- 
nated  horse  blood  agar  plates,  the  intraperitoneal  inocula- 
tion of  white  mice  with  specimens  of  sputum  according  to 
the  method  described  by  Blake1  for  the  determination  of 


VBlake:     Jour.    Exper.    Med.,    1917,   xxvi,   67. 

51 


52         PNEUMONIAS  AND   INFECTIONS  OF   RESPIRATOR1'   TRACT 

pneumococcus  types,  and  in  some  cases  the  method  of 
Awry.-  B.  influenzas  pneumococci  and  hemolytic  strep- 
tococci were  identified  by  the  methods  described  elsewhere. 
Note  was  made  in  most  instances  of  the  presence  of  other 
organisms  such  as  members  of  the  Gram-negative  ftiplo- 
coccus  group,  staphylococci,  diphtheroids,  and  members  of 
the  streptococcus  viridans  group,  but  no  attempl  was  made 
to  further  isolate  or  identify  them  since  they  played  no  sig- 
nificant pari  in  the  cases  studied  except  in  rare  instances. 

Influenza 

The  fall  epidemic  of  influenza  at  Camp  Pike  began  about 
September  1,  1918,  and  reached  epidemic  proportions  on 
September  23  when  214-  cases  were  admitted  to  the  base 
hospital.  The  epidemic  was  at  its  height  from  September 
27  to  October  3,  during  which  period  there  were  in  the 
neighborhood  of  1,000  new  cases  daily.  From  this  date  un- 
til October  31  the  number  of  new  cases  occurring  daily 
steadily  decreased  and  by  the  latter  date  the  epidemic  was 
over.  Scattered  cases  continued  to  occur,  however,  through- 
out November,  and  during  the  last  week  of  this  month  and 
the  first  week  of  December  a  second  epidemic  wave  of  rela- 
tively mild  character  occurred.  From  September  1  to  Octo- 
ber 3]  the  total  number  of  cases  of  influenza  reporting  sick 
was  12,393.  During  the  same  period  there  were  1,499  cases 
of  pneumonia  with  46(3  deaths. 

Influenza  as  observed  at  Camp  Pike  differed  in  no  es- 
sential respects  from  that  occurring  elsewhere.  In  brief, 
it  presented  itself  as  a  highly  contagious,  self -limited  infec- 
tious disease  of  relatively  short  duration  in  most  instances, 
the  principal  manifestations  of  which  were  sudden  onset 
with  high  fever,  profound  prostration,  severe  aching  pains 
in  back  and  extremities,  conjunctival  injection,  flushing  of 
the  face,  neck,  and  upper  thorax  often  amounting  to  a  true 
erythema,  and  a  rapidly  progressing  attack  upon  the  mu- 


-Avcry:     Jour.   Am.   Med.   Assn.,   191S,  Ixx,   1". 


CLINICAL   FEATURES  AND   BACTERIOLOGY   OF   I  X  KLI'KXZA        .)■> 

cous  membranes  of  the  respiratory  tract  as  manifested  by 
coryza,  pharyngitis,  tracheitis  and  bronchitis  with  a 
marked  tendency  to  hemorrhage;  in  itself  it  is  rarely  se- 
rious, but  in  reality  serious  because  of  the  large  number  of 
individuals  attacked  and  temporarily  incapacitated  and  be- 
cause it  predisposed  to  widespread  and  highly  fatal  sec- 
ondary infection  of  the  lungs. 

Clinical  Features. — A  clinical  study  of  100  consecutive 
cases  of  influenza  admitted  during  the  height  of  the  epi- 
demic was  made. 

The  onset  was  sudden,  in  most  instances  being  initiated 
with  marked  sensations  of  chilliness  in  82  cases.  Although 
a  severe  chill  was  probably  relatively  uncommon,  44  of  these 
patients  considered  the  symptom  of  sufficient  severity  to 
describe  it  as  such.  This  was  accompanied  by  extreme  gen- 
eral malaise  with  severe  aching  pains  throughout  the  whole 
body.  Intense  backache  was  complained  of  in  40  cases, 
headache  in  54  cases.  A  varying  degree  of  prostration, 
sometimes  leading  to  complete  collapse,  was  almost  uni- 
versal ;  5  patients  complained  of  extreme  asthenia  and  2 
of  marked  dizziness.  At  time  of  admission  to  the  hospital 
the  face,  neck  and  upper  chest  exhibited  a  uniform  eryth- 
ematous flush,  never  macular  in  appearance.  The  conjunc- 
tivae were  deeply  injected,  but  lacrimation  was  not  notice- 
able and  a  true  exudative  conjunctivitis  was  not  encoun- 
tered. Onset  was  accompanied  by  a  sharp  elevation  of  tem- 
perature ranging  from  100°F.  to  106°  F.,  in  most  cases  be- 
ing between  102°  F.  and  105°  F.,  at  the  time  of  admission. 
No  constant  type  of  temperature  curve  was  maintained. 
Excluding  the  15  cases  in  this  group  that  developed  pneu- 
monia, the  temperature  was  well  sustained  throughout  the 
course  of  the  disease  in  46,  irregular  in  33,  and  definitely 
remittent  in  6.  The  duration  of  the  fever  varied  between 
one  and  seven  days,  the  temperature  having  returned  to 
normal  in  all  but  19  of  the  85  cases  by  the  end  of  four  days. 
The  duration  of  fever  was  one  dav  in  18  cases,  two  days  in 


54        PNEUMONIAS  AND  INFECTIONS  OF  RESPIRATORS  TRACT 

12,  three  .lays  in  19,  four  days  in  17,  five  days  in  10,  six 
days  in  4,  and  seven  days  in  5.  Of  the  4  cases  with  fever 
for  six  days,  2  had  a  fairly  extensive  bronchitis,  1  a  laryn- 
gitis. Of  the  5  eases  with  lexer  of  seven  days'  duration,  3 
had  signs  of  an  extensive  bronchitis,  2  of  only  a  mild  bron- 
chitis. 

The  pulse  was  relatively  slow  in  rate  as  compared  with 
the  degree  of  temperature  elevation,  running  between  90 
and  100  heats  per  minute  in  the  large  majority  of  cases. 
At  the  height  of  the  disease  it  was  full  and  easily  com- 
pressed. No  irregularities  were  noticed.  With  recovery 
it  fell  promptly  to  normal.  The  respiratory  rate  showed 
only  moderate  elevation,  being  between  20  and  26  in  most 
cases.  In  a  few  instances  a  rate  as  high  as  32  was  recorded 
at  time  of  admission  to  the  hospital,  but  this  promptly  fell 
with  rest  in  bed.  A  respiratory  rate  rising  above  26  after 
the  third  or  fourth  day  of  the  disease  nearly  always  indi- 
cated a  beginning  pneumonia.  With  recovery  the  rate 
promptly  fell  to  normal.  Cyanosis  did  not  occur  in  the 
absence  of  pneumonia. 

Aside  from  the  manifestations  of  a  profound  toxemia, 
influenza  was  preeminently  characterized  by  symptoms  of 
respiratory  tract  infection.  The  appearance  of  respiratory 
symptoms  occurred  at  varying  intervals  after  the  onset  of 
the  disease,  being  well  developed  by  the  end  of  twenty-four 
hours  in  most  cases.  A  progressive  attack  upon  the  mu- 
cous membranes  of  the  respiratory  tract  was  universal,  be- 
ginning with  coryza  and .  pharyngitis  and  progressing  to 
tracheitis  or  vice  versa.  Further  extension  of  the  infection 
to  the  bronchi,  however,  Mas  by  no  means  universal,  49 
cases  in  the  group  studied  recovering1  without  developing 
evidence  of  bronchitis.  Sore  throat  was  rarely  complained 
of,  and  laryngitis,  possibly  due  to  secondary  infection,  oc- 
curred only  once.  The  progress  of  the  infection  was  marked 
subjectively  by  sensations  of  irritation,  stinging,  and  a  feel- 
ing  of  tightness.  A  profuse,  thin,  mucoid  exudate  appeared; 


CLINICAL  FEATURES  AND  BACTEHIOLOG'X   OF   I  XKU'KXXA        55 

the  pharyngeal  walls  and  the  soft  palate  showed  a  charac- 
teristic deep  red  granular  appearance.  The  onset  of  tra- 
cheitis began  with  a  sense  of  burning  and  tightness  beneath 
the  sternum  accompanied  by  a  harassing  cough,  at  first  non- 
productive, later  with  the  outpouring  of  an  exudate  becom- 
ing productive.  The  sputum  varied  in  character  between  a 
scanty,  thin,  mucoid  sputum  and  a  profuse,  frankly  puru- 
lent sputum  in  cases  subsequently  developing  an  extensive 
bronchitis.  Hemorrhage  from  the  mucous  membranes  was 
common.  Epistaxis  occurred  in  12  per  cent  of  the  cases 
and  was  often  profuse.  The  sputum  contained  fresh  blood 
in  varying  amounts  in  24  per  cent  of  the  cases ;  51  per  cent 
of  the  cases  developed  signs  of  bronchitis.  In  15  of  these 
the  bronchitis  was  mild,  probably  limited  to  the  larger 
bronchi,  physical  examination  showing  only  inconstant  sibi- 
lant and  musical  rales.  The  sputum  in  these  cases  was 
neither  profuse  nor  frankly  purulent;  36  cases  developed  a 
fairly  extensive  purulent  bronchitis  as  manifested  by  more 
or  less  diffusely  scattered  moist  rales  and  by  moderately 
copious  mucopurulent  or  frankly  purulent  sputum.  This 
bronchitis  was  not  accompanied  by  an  increase  in  the  re- 
spiratory rate  or  by  cyanosis  unless  pneumonia  subse- 
quently developed. 

Gastrointestinal  symptoms  were  insignificant :  8  patients 
complained  of  nausea  early  in  the  disease  and  6  of  them 
vomited.  Diarrhea  occurred  in  only  1  case,  constipation 
being  the  rule.  The  spleen  was  palpable  in  21  cases,  but 
this  is  of  doubtful  significance,  since  nearly  all  the  patients 
came  from  malarial  regions.  Jaundice  was  not  noted. 
Aside  from  the  profound  depression,  sometimes  amounting 
to  stupor,  mental  symptoms  were  not  noted  except  in  1 
case  which  showed  a  mild  delirium. 

Influenza,  although  per  se  a  self -limited  disease  of  short 
duration,  frequently  leads  to  the  development  of  serious 
complications,  the  most  important  of  which  are  pneumonia 
and  purulent  bronchitis  with  a  varying  degree  of  bronchi- 


56         PNEUMONIAS   AND   IMITATIONS  OF   RESPIRATOR?  TRACT 

ectasis.  In  the  group  of  UK)  cases  of  influenza  studied,  pur- 
ulent bronchitis  developed  in  36  instances,  pneumonia  in 
15;  in  3  eases  there  was  lobar  pneumonia,  in  L2  broncho- 
pneumonia. Further  dismission  of  these  complications  is 
reserved  for  the  sections  dealing  with  them  in  detail.  Other 
complications  were  relatively  rare,  otitis  media  occurred 
in  one  ease  and  frontal  sinusitis  in  one.  No  fatalities  were 
observed  among  eases  of  uneonipl ieated  influenza,  the 
deaths  that  occurred  being  invariably  associated  with  a 
secondary  pneumonia  due  in  nearly  all  instances  to  sec- 
ondary infection  with  pneumoeoeei  or  hemolytic  strepto- 
cocci. 

Purulent  Bronchitis 

It  has  been  stated  that  a  considerable  number  of  cases 
of  influenza  developed  a  more  or  less  extensive  purulent 
bronchitis.  This  term  is  used  as  descriptive  of  a  group  of 
cases  showing  clinically  evidence  of  a  diffuse  bronchitis  as 
manifested  by  numerous  medium  and  fine  moist  rales  scat- 
tered throughout  the  chest  and  evidence  of  a  definitely  pu- 
rulent inflammatory  reaction  as  indicated  by  the  expectora- 
tion of  fairly  copious  amounts  of  mucopurulent  or  frankly 
purulent  sputum.  This  condition  is  regarded  as  quite  dis- 
tinct, on  the  one  hand,  from  the  common  type  of  mucoid 
bronchitis  frequently  associated  with  "common  colds"  and 
a  fairly  common  feature  of  uncomplicated  cases  of  influ- 
enza, in  which  physical  examination  of  the  chest  reveals 
only  transient  sibilant  and  musical  rales  without  evidence 
of  extension  to  finer  bronchi,  and,  on  the  other  hand,  from 
bronchopneumonia. 

Bacteriology. — Thirteen  cases  of  purulent  bronchitis  fol- 
lowing influenza  in  none  of  which  was  there  any  evidence  of 
pneumonia  at  the  time  cultures  of  the  'sputum  were  made 
nor  later  were  subjected  to  careful  bacteriologic  study. 
Specimens  of  bronchial  sputum  were  collected  in  sterile 
Petri  dishes  and  selected  portions  thoroughly  washed  to 
remove   surface    contaminations   before   bacteriologic    ex- 


CLINICAL  FEATURES  AND   BACTERIOLOGY  OF   INFLUENZA 


:>( 


aminations  were  made.     The  results  arc  shown   in   Table 
XIII. 

Table  XIII 

Bacteriology  of  the  Sputum  in  Cases  of  Purulent   Bronchitis    Follow- 
ing Influenza 


CASE 

STAINED    FILM    OF 
SPUTUM 

DIRECT  CULTURE  ON 
BLOOD    AGAR   PLATE 

MOUSE     INOCULATION 

GJ 

B.   influenzae  4-4-4- 

B.  influenzae  4-4-4-4- 

B.  influenzae 

Gram  +  diplococci  4- 

Pneumococcus  4- 

J'licuinococcus 

(type    undcterminfd ) 

WAL 

B.   influenzas  +  4- 

B.   influenzae  4-4-4- 

— 

Gram  +  diplococci  +  4- 

Pneumococcus  IV  4-  4- 

TH 

B.  influenzae  4-4-4- 

B.  influenzae  4-4-4-4- 

— 

Gram  +  diplococci  4-4-4- 

Pneumococcus  IV  4-  4- 

LH 

B.  influenzae  4- 

B.   influenzae  4-4- 

— 

Gram  +  diplococci  4- 

Pneumocoecus  IV  4-4- 

FBD 

Gram  +  diplococci  4-4-4-4 

Pneumococcus  IV  4-4-4- 

Pneumococcus   IV 

B.  influenzae  4- 

B.  influenzae 

Wa 

B.   influenzae  4-  4- 

B.   influenzae  4-4- 

— 

Gram  4-  diplococci  4-  4- 

Pneumococcus  IV  4-  4- 

Sh 

B.  influenzae  4-4-4- 

B.    influenzae  4-4- 

•  — 

Gram  4-  diplococci  4-4- 

Pneumococcus  IV  4-4-4- 

Wal 

Gram  4-  diplostrep  4  4-4- 

S.  viridans  4-4- 

— 

B.  influenzae  4- 

B.  influenzae  4-  4- 

CLF 

B.  influenzae  4-4-4-4-4- 

— 

B.  influenzae 

Gram  4-  diplococci  4- 

Pneumococcus  IV 

NCC 

B.   influenzae  4-4- 

B.   influenzae  4-4-4- 

B.   influenzae 

Gram  -  micrococcus  4- 

M.  eatarrhalis  4-4- 

M.   eatarrhalis 

Gram  4-  diplostrep.  4- 

S.  viridans  4-4- 

JCM 

B.   influenzae  4-4-4- 

B.  influenzae  4-4-4-4- 

B.  influenzae 

Gram  4-  streptococcus  4- 

S.   hemolyticus  4- 

S.  hemolyticus 

Gram  —  micrococcus  4- 

M.  eatarrhalis  4- 

Pneumococcus  IV 

Gram  4-  diplococcus  4- 

Bl 

B.  influenzae  4- 

— 

B.  influenzae 

Gram  4-  diplococcus  4- 

Pneumococcus  Ila 

Bu 

B.  influenzae  4-4-4-4- 

B.   influenzae  4-4-4- 

B.  influenzae 

Gram  4-  diplococcus  4-4-4-4- 

Pneumococcus  IV  4-4-4- 

Pneumococcus   TV 

From  the  data  presented  in  Table  XIII  it  is  evident  that 
a  mixed  infection  existed  in  all  cases.  The  results  obtained 
by  stained  sputum  films  and  by  direct  culture  on  blood  agar 
plates  are  of  special  significance.  B.  influenzae  was  present 
in  all  cases,  being  the  predominant  organism  in  6  cases, 
abundantly  present  in  others,  and  few  in  number  in  2. 
Of  other  organisms  the  pneumococcus  was  most  frequently 
found,  occurring  in  11  of  the  13  cases,  in  all  but  2  instances 
being  present  in  considerable  numbers.  S.  viridans  was  en- 
countered twice,  once  in  association  with  a  Gram-negative 


micrococcus  resembling  M.  eatarrhalis  culturally.  S.  hem- 
olyticus  was  found  oner,  together  with  M.  eatarrhalis  and 
a  few  pneumococci,  Type  IV,  coming  through  in  the  mouse 
only  and  of  doubtful  significance.  The  stained  sputum 
films  and  direct  cultures  always  showed  these  organisms 
present  in  sufficient  abundance  to  indicate  that  they  were 
present  in  the  bronchial  sputum  and  wore  not  merely  con- 
taminants from  the  buccal  mucosa. 

It  seems  quite  probable  from  these  results  that  purulent 
bronchitis  following  influenza  is,  in  most  cases  at  least,  due 
to  mixed  infection  of  the  bronchi  and  should  be  looked  upon 
as  a  complication  of  influenza.  Whether  the  condition  may 
be  caused  by  infection  with  B.  influenza?  alone  is  difficult 
to  say.  No  evidence  that  it  may  be  caused  by  B.  influenza1 
alone  was  obtained  in  the  cases  studied.  It  is  not  intended 
to  enter  here  into  a  discussion  as  to  whether  B.  influenza? 
should  be  regarded  as  a  secondary  invader  or  not;  the  other 
organisms  encountered  certainly  are.  It  would  seem  most 
probable  that  purulent  bronchitis  is  caused  by  the  mixed 
infection  of  B.  influenza?  and  various  other  organisms,  com- 
monly the  pneumococcus,  but  that  the  condition  is  initiated 
by  the  invasion  of  the  bronchi  by  these  other  organisms  in 
the  presence  of  a  preceding  infection  with  B.  influenza?. 

Clinical  Features. — Purulent  bronchitis  following  in- 
fluenza began  insidiously  without  any  prominent  symptoms 
to  mark  its  onset.  About  the  third  or  fourth  day  of  in- 
fluenza, when  recovery  from  the  primary  disease  might  be 
looked  for,  the  patient  would  begin  to  cough  more  fre- 
quently, raising  increasing  amounts  of  mucopurulent 
sputum.  This  sputum  was  yellowish  green  in  color,  copious 
in  amount,  and  often  somewhat  nummular  in  character, 
sometimes  streaked  with  blood.  These  symptoms  were  ac- 
companied by  the  appearance  of  coarse,  medium  and  fine 
moist  rales  more  or  less  diffusely  scattered  throughout 
the  chest  and  usually  most  numerous  over  the  lower  lobes. 
The  percussion  note,  breath  and  voice  sounds,  and  vocal 


CLINICAL  FEATURES  AND  BACTERIOLOGY  OF   I  X  FU'KNZA        59 

and  tactile  fremitus  remained  normal.  There  was  no 
increase  in  the  respiratory  rate  or  pulse  rate,  and  cya- 
nosis did  not  develop  in  the  absence  of  a  beginning  pneu- 
monia. Many  such  cases,  of  course,  developed  broncho- 
pneumonia; in  this  event  areas  showing1  diminished  reso- 
nance, suppressed  breath  sounds,  and  fine  crepitant  rales 
with  the  "close  to  the  ear"  quality  would  appear,  the  res- 
piratory rate  would  become  increased  and  cyanosis  would 
become  evident.  In  those  cases  of  purulent  bronchitis 
not  developing  pneumonia,  a  moderate  elevation  of  tem- 
perature, rarely  above  101°  F.,  and  irregular  in  character 
usually  occurred  and  persisted  for  a  few  days  or  a  week. 

Many  cases  maintained  a  persistent  cough,  raising  con- 
siderable amounts  of  sputum  throughout  the  period  of  their 
convalescence  in  the  hospital,  which  was  often  considerably 
prolonged  when  this  complication  of  influenza  occurred. 
Although  no  clinical  data  are  available  on  such  cases  over 
a  prolonged  period  of  observation,  it  seems  probable  that 
some  of  them,  at  least,  had  developed  some  degree  of  bron- 
chiectasis. This  would  seem  all  the  more  probable,  since 
many  cases  of  pneumonia  following  influenza  showed  at 
autopsy  extensive  purulent  bronchitis  with  well-developed 
bronchiectasis.  Bronchiectasis  will  be  discussed  in  greater 
detail  in  another  section  of  this  report.  It  is  this  group 
of  cases  with  more  or  less  permanent  damage  to  the  bron- 
chial tree  that  makes  this  type  of  bronchitis  following  in- 
fluenza a  serious  complication  of  the  disease. 

PNEUMONIA 

The  opportunity  presented  for  a  correlated  study  of  the 
clinical  features,  bacteriology,  and  pathology  of  pneumonia 
following  influenza  throughout  the  period  of  the  epidemic 
at  Camp  Pike  from  September  6,  1918,  to  December  15, 
1918,  made  it  evident  that  this  pneumonia  could  be  regarded 
as  an  entity  in  only  one  respect,  namely,  that  influenza  was 
the  predisposing  cause.     Clinically,  bacteriologically,  and 


GO         PNEUMONIAS  AND   INFECTIONS  OF   RESPIRATORY  TRACT 

pathologically  ii  presented  a  very  diversified  picture  rang- 
ing all  the  way  from  pneumococcal  lobar  pneumonia  to 
hemolytic  streptococcus  interstitial  and  suppurative  pneu- 
monia with  the  picture  modified  to  a  varying  extenl  by  the 
preceding  or  concomitant  influenzal  infection. 

One  hundred  and  eleven  consecutive  eases  in  which  care- 
ful clinical  and  bacteriologic  studies  were  made  form  the 
basis  of  the  material  presented.  Of  these  cases,  38  came  to 
necropsy  so  that  ample  opportunity  was  presented  to  cor- 
relate the  clinical  and  bacteriologic  studies  made  during 
life  with  the  pathology  and  bacteriology  at  necropsy.  It 
has  seemed  advisable  to  group  the  eases  primarily  on  an 
etiologic  basis  with  secondary  division  according  to  clinical 
features  in  so  far  as  this  can  be  done.  Bacteriologic  studies 
showed  that  at  the  time  of  onset  these  pneumonias  were 
either  pneumococcus  pneumonias  or  mixed  pneumococcus 
and  influenza  bacillus  pneumonias  in  nearly  all  instances. 
Certain  of  these  cases  later  became  complicated  by  a  super- 
imposed hemolytic  streptococcus  or  a  staphylococcus  in- 
fection. In  a  few  instances  hemolytic  streptococcus 
pneumonia  directly  followed  influenza  Avithout  an  interven- 
ing pneumococcus  infection.  B.  influenzre  was  present  in 
varying  numbers  in  nearly  all  cases.  In  only  2  instances 
however,  was  it  found  unassociated  with  pneumococci  or 
hemolytic  streptococci,  once  alone  and  once  with  S.  viridans. 

Clinically  the  cases  fell  into  four  main  groups  :  (1)  Lobar 
pneumonia;  (2)  lobar  pneumonia  with  purulent  bronchitis; 
(3)  bronchopneumonia  (pneumococcus)  ;  (4)  bronchopneu- 
monia (streptococcus).  It  should  be  borne  in  mind,  how- 
ever, that  the  picture  was  a  complex  one  and  that  cor- 
rect clinical  interpretation  was  not  always  possible,  since 
many  cases  did  not  conform  sharply  to  any  one  type  and 
superimposed  infections  during  the  course  of  the  disease 
often  modified  the  picture. 

Pneumococcus  Pneumonia  Following  Influenza.  —Bacte- 
riologic examination  of  selected  and  washed  specimens  of 


CLINICAL  FEATUEES  AND   BACTERIOLOGY  OF   I  X  FL1  'KXZA       ( i  1 

sputum  coughed  from  the  lungs  at  time  of  onset  of  pneu- 
monia showed  the  various  immunologic  types  of  pneumo- 
coccus  to  be  present  in  105  cases.  The  incidence  of  the 
different  types  is  shown  in  Table  XIV. 


Tabli 

XIV 

Types  of  Pneumococcus 

in  105  Cases  of  Pneumococcus   Pneumonia    Fol- 

lowing Influenza 

lobar 

pneumonia 

BRONCHO- 
PNEUMONIA 

TOTAL 

PES    CENT 

Pneumococcus,  Type  I 

8 

0 

8 

7:6 

Pneumococcus,   Type  II 

3 

1 

4 

3.8 

Pneumococcus,  II  atyp. 

12 

7 

9 

18.1 

Pneumococcus,   Type  III 

3 

3 

6 

5.7 

Pneumococcus,  Group  IV 

32 

36 

68 

64.8 

The  most  noteworthy  feature  of  the  figures  in  Table  XIV 
is  the  high  proportion  of  pneumonias  due  to  types  of  pneu- 
mococci  found  in  the  mouths  of  normal  individuals,  93  cases 
or  88,6  per  cent,  being  caused  by  Pneumococcus  Types  II 
atypical,  III,  and  TV.  This  is  in  harmony  with  the  results 
generally  reported  and  is  in  all  probability  due  to  the  fact 
that  in  patients  with  influenza  pneumococci,  which  under 
normal  conditions  would  fail  to  cause  pneumonia,  readily 
gain  access  to  the  respiratory  tract  and  produce  the  disease. 
It  is  also  of  interest  that  with  one  exception  the  highly 
parasitic  pneumococci  of  Types  I  and  II  were  associated 
with  pneumonias  clinically  lobar  in  type. 

Superimposed  infection  of  the  lungs  with  other  types  of 
pneumococci  than  those  primarily  responsible  for  the  de- 
velopment of  pneumonia  occurred  not  infrequently  in  this 
group  of  cases  either  during  the  course  of  the  disease  or 
shortly  after  recovery  from  the  first  attack  of  pneumonia. 
Pneumococcus  Type  II  infection  was  superimposed  upon 
or  shorthT  followed  pneumonia  caused  by  Group  IV  pneu- 
mococci in  4  instances,  by  Pneumococcus  II  atypical  in  1 
instance.  In  1  case  pneumonia  due  to  Pneumococcus  II 
atypical  occurred  three  days  after  recovery  from  a  Pneu- 
mococcus Type  I  pneumonia,  in  another  case  Pneumococcus 


62         PNEUMONIAS  -VXD  IXFECTIOXS  OF  RESPIRATORY  TRACT 

Typo  111  infection  was  superimposed  upon  a  pneumonia  or- 
iginally due  to  a  pneumococcus  <>l'  Group  IV.  Those  cases 
are  presented  in  detail  in  another  section  of  this  report, 
and  in  several  instances  were  shown  to  ho  directly  due  to 
contact    infection    from   patients  in   neighboring  beds. 

In  a  similar  manner,  superimposed  infection  with  S. 
hemolyticus  at  some  time  during  the  course  of  the  pneu- 
monia, occurred  in  1',)  cases  in  this  group,  with  fatal  result 
in  all  %ut  one.  Streptococcus  infection  occurred  in  pneu- 
monia duo  to  Pneumococcus  II  atypical  once,  to  Pneumo- 
coccus Type  III  once,  and  to  pneumococci  of  Group  IV 
eleven  times.  Nine  of  these  cases  were  free  from  hemo- 
lytic streptococci  at  the  time  of  onset  of  the  pneumonia, 
4  showed  a  very  few  colonies  of  hemolytic  streptococci  in 
the  first  sputum  culture  made. 

B.  influenzae  was  found  in  the  sputum  coughed  from  the 
deeper  air  passages  in  the  majority  of  cases,  being  present 
in  80,  or  76.2  per  cent,  of  the  105  cases.  In  the  58  cases 
of  lobar  pneumonia  it  was  found  41  times,  or  70.7  per  cent, 
in  the  47  cases  of  bronchopneumonia  39  times,  or  82.9  per 
cent.  The  abundance  of  B.  influenza?  in  the  sputum  varied 
greatly  in  different  cases.  Microscopic  examination  of 
stained  sputum  films  and  direct  culture  of  the  sputum  on 
blood  agar  plates  showed  that  in  general  it  was  more  abun- 
dant in  the  mucopurulent  sputum  from  cases  of  broncho- 
pneumonia than  in  the  mucoid  rusty  sputum  from  cases 
of  lobar  pneumonia.  This  was  by  no  means  an  invariable 
rule,  however,  since  in  the  former  the  bacilli  were  some- 
times very  few  in  number,  in  the  latter  quite  abundant. 
Whether  B.  influenza?  shared  in  the  production  of  the  actual 
pneumonia  in  these  cases  is  difficult  to  decide  and  cannot 
be  stated  on  the  basis  of  the  bacteriologic  and  clinical  ob- 
servations which  have  been  made. 

Clinical  Features. — One  of  the  most  striking  aspects  of 
pneumococcus  pneumonia  following  influenza  was  the 
diversity  of  clinical  pictures  presented.     These  varied  all 


CLINICAL  FEATURES  AND  BACTERIOLOGY  OF  INFLUENZA        63 

the  way  from  the  classical  picture  of  lobar  pneumonia  to 
that  of  bronchopneumonia  of  all  grades  of  severity  from 
the  rapidly  fatal  coalescing  type  to  that  of  very  mild  char- 
acter with  very  slight  signs  of  consolidation.  For  this 
reason  it  is  questioned  whether  there  is  any  real  justifica- 
tion for  speaking  of  a  typical  influenzal  pneumonia,  an 
opinion  that  seems  well  supported  by  the  diversified  picture 
found  at  the  necropsy  table. 

For  purposes  of  presentation,  pneumococcus  pneumonia 
following  influenza  may  be  divided  into  three  clinical 
groups:  (1)  Lobar  pneumonia;  (2)  lobar  pneumonia  with 
purulent  bronchitis;  (3)  bronchopneumonia.  No  accurate 
data  are  available  as  to  the  relative  frequency  with  which 
these  three  types  occurred  at  Camp  Pike.  In  the  group  of 
105  cases  studied  there  were  58  cases  of  lobar  pneumonia,  11 
of  which  had  purulent  bronchitis,  and  47  cases  of  broncho- 
pneumonia. The  majority  of  these  cases,  however,  oc- 
curred during  the  early  days  of  the  epidemic  of  influenza 
and  probably  show  a  considerably  higher  proportion  of 
lobar  pneumonias  than  actually  occurred  in  the  total  num- 
ber of  pneumonias  throughout  the  epidemic.  This  is  indi- 
cated by  the  fact  that  of  100  consecutive  cases  of  influenza 
selected  for  observation  at  the  height  of  the  epidemic,  3  de- 
veloped clinical  evidence  of  lobar  pneumonia  and  12  of 
bronchopneumonia. 

(1)  Lobar  pneumonia  presenting  the  typical  clinical  pic- 
ture with  sudden  onset,  tenacious  rusty  sputum,  sustained 
temperature,  and  physical  'signs  of  complete  consolidation 
of  one  or  more  lobes  occurred  in  47  cases ;  36  cases  in  this 
group  definitely  followed  influenza.  In  11  cases  no  certain 
clinical  evidence  of  a  preceding  influenza  was  obtained,  and 
it  is  probable  that  some  of  these  represent  cases  of  pneu- 
monia occurring  independently  of  the  epidemic  of  influenza. 

The  onset  of  pneumonia  in  this  group  of  cases  occurred 
from  four  to  nine  claj^s  after  the  onset  of  influenza  and  with 
few  exceptions  was  ushered  in  b}^  a  chill  and  pain  in  the 


64         PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATORS   TRACT 

chest.  In  several  instances  the  patienl  had  apparently  re- 
covered from  influenza  as  evidenced  by  fall  of  temperature 
to  normal.  A  Pter  twenty-four  to  seventy-1  wo  hours  of  nor- 
mal temperature  the  patient  would  have  a  chill  and  develop 
lobar  pneumonia.  In  the  majority  of  eases,  however,  lobar 
pneumonia  developed  while  the  patient  was  still  sick  with 
influenza.  The  course  of  the  disease,  symptomatology 
and  physical  signs  were  quite  characteristic  of  lobar  pneu- 
monia and  require  no  special  comment.  Recovery  by  crisis 
occurred  in  21  eases,  by  lysis  in  8.  Pneumococcus  empyema 
developed  in  3  cases,  fibrinopurulenl  pericarditis  in  3  and 
all  but  1  ol*  these  (!  eases  terminating  fatally. 

In  Table  XV  5  fatal  eases  of  lobar  pneumonia,  which 
illustrate  some  of  the  unusual  features  of  the  disease  when 
it  follows .  influenza,  have  been  summarized.  The  first  2 
cases  represent  examples  of  recurring'  attacks  of  pneu- 
monia which  developed  shortly  after  recovery  from  the 
first  attack,  in  both  instances  being  due  to  types  of  pneu- 
mococci  different  from  those  causing  the  first  attack.  The 
third  case  represents  an  example  of  superimposed  infection 
of  the  lungs  with  hemolytic  streptococci  and  staphylococci 
during  the  course  of  a  pneumonia  due  to  Pneumococcus  IV 
and  disappearance  of  the  latter  organism  from  the  tissues 
so  that  it  was  not  found  at  time  of  necropsy.  The  last 
2  cases  are  examples  of  fulminating  rapidly  fatal  cases  of 
lobar  pneumonia  associated  with  mixed  infections  of  pneu- 
mococci  and  hemolytic  streptococci,  the  streptococci  prob- 
ably being  secondary  in  both  cases.  Cases  like  the  few 
examples  cited  above,  which  occurred  not  infrequently 
throughout  the  epidemic  of  influenza,  serve  to  illustrate 
the  difficulties  which  may  be  met  in  attempting  to  corre- 
late the  clinical,  bacteriologic  and  pathologic  features  of 
pneumonia  following  influenza  unless  careful  bacteriologic 
examinations  are  made  both  during  life  and  at  the  necropsy 
table  in  the  same  group  of  cases. 


CLTNTCAL  FEATURES  AND  BACTERIOLOGY  OF   I  N  FL1 1  KX/A       65 


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()(i        PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATOR'S  TRACT 

(2)  There  were  11  eases  of  lobar  pneumonia  with  puru- 
lent bronchitis  in  the  group  studied.  Clinically,  they 
closely  resembled  the  eases  in  the  preceding  group  except 
in  so  far  as  the  picture  was  modi  lied  by  the  presence  of  the 
purulent  bronchitis.  All  directly  followed  influenza.  The 
sputum,  instead  of  being  rusty  and  tenacious,  was  profuse 
and  mucopurulent,  usually  streaked  with  blood.  Stained 
films  and  direct  culture  on  Mood  agar  plates  showed  pneu- 
mococcal in  abundance  and  B.  influenzae  in  varying  numbers, 
in  only  two  instances  the  predominant  organism.  The 
physical  signs  were  those  of  lobar  pneumonia  with,  in  addi- 
tion, those  of  a  diffuse  bronchitis  as  manifested  by  medium 
and  coarse  moist  rales  throughout  both  chests.  Five  cases 
recovered  by  crisis;  6  terminated  fatally  and  in  all  of  them 
the  clinical  diagnosis  of  lobar  pneumonia  with  purulent 
bronchitis  was  confirmed  at  necropsy. 

(3)  Forty-seven  cases  in  the  group  studied  presented  the 
clinical  picture  of  bronchopneumonia.  The  onset  of  pneu- 
monia in  these  cases  was  in  most  instances  insidious  and 
appeared  to  occur  as  a  continuation  of  the  preceding  in- 
fluenza. The  temperature,  instead  of  falling  to  normal 
alter  from  three  to  four  days,  remained  elevated  or  rose 
higher,  the  respiratory  rate  began  to  rise,  a  moderate  cya- 
nosis appeared,  the  cough  increased,  and  the  sputum 
became  more  profuse,  usually  being  mucopurulent  and 
blood  streaked,  sometimes  mucoid  with  fresh  blood.  The 
pulse  showed  little  change  at  first,  being  only  moderately 
accelerated.  Pleural  pain,  so  characteristic  of  the  onset  of 
lobar  pneumonia,  was  rarely  complained  of,  but  a  certain 
amount  of  substernal  pain  was  common,  probably  due  to 
the  severe  tracheobronchitis.  Physical  examination  at  this 
time  revealed  small  areas  showing  relative  dullness,  •di- 
minished or  nearly  absent  breath  sounds,  and  fine  crepitant 
rales.  These  areas  usually  appeared  first  posteriorly  over 
the  lower  lobes. 


CLINICAL  FEATURES  AND   BACTERIOLOGY  OE   I  X  I- 'LI  I  KXZA       61 

The  subsequent  course  of  the  disease  showed  the  widest 
variation  from  mild  cases  with  limited  pulmonary  involve- 
ment going  on  to  prompt  recovery  in  four  or  five  days  with 
defervescence  by  lysis  or  crisis  to  those  presenting  the  pic- 
ture of  a  rapidly  progressive  and  coalescing  pneumonia 
with  fatal  outcome.  In  the  milder  cases  the  diagnosis  of 
pneumonia  depended  in  considerable  part  upon  the  general 
symptoms  of  continued  fever,  increased  respiratory  rate, 
and  slight  cyanosis.  Definite  pulmonary  signs  were  always 
present  if  carefully  looked  for,  though  sometimes  not  out- 
spoken. Areas  of  bronchial  breathing  and  bronchophony 
often  appeared  late,  sometimes  not  until  the  patient  was 
apparently  recovering.  In  the  severe  cases  cyanosis  be- 
came intense  and  an  extreme  toxemia  dominated  the  pic- 
ture. In  certain  of  these  cases  there  was  an  intense  pul- 
monary edema.  The  respiratory  rate  showed  wide  varia- 
tion, the  breathing  in  some  cases  being  rapid  and  gasping, 
in  others  comparatively  quiet.  Progressive  involvement 
of  the  lungs  occurred  with  the  development  of  marked  dul- 
ness,  loud  bronchial  breathing  and  bronchophony.  Abun- 
dant medium  and  coarse  moist  rales  were  heard  throughout 
the  chest,  probably  due  in  considerable  part  to  the  exten- 
sive bronchitis  almost  universally  present.  An  active  de- 
lirium was  not  uncommon.  Signs  of  pleural  involvement, 
even  in  the  most  severe  and  extensive  cases,  rarely  occurred, 
except  in  those  cases  in  which  a  hemolytic  streptococcus 
infection  supervened. 

Of  the  47  cases  in  this  group,  29  recovered ;  14  by  crisis, 
15  by  lysis.  The  average  duration  of  illness  from  the  onset 
of  influenza  until  recovery  from  the  pneumonia  was  ten 
days,  the  majority  of  these  cases  being  relatively  mild  in 
character  with  pneumonia  of  three  to  six  days'  duration. 
Empyema  with  ultimate  recovery  occurred  in  1  of  these 
cases,  Pneumococcus  Type  II  being  the  causative  organism. 

There  were  18  fatal  cases  in  the  group.  Nine  of  these 
are  summarized  in  Table  XVI  as  illustrative  of  the  fre- 


68        PNEUMONIAS  AXli   ixrr.crioxs  OF   RESPIRATORS  TRACT 

quently  complex  character  of  bronchopneumonia  following 
influenza  and  because  of  the  interest  attaching  to  the  bac- 
teriologic  examinations  made  during  life  and  at  necropsy. 
Case  70  is  a  typical  instance  of  the  rapidly  progressive 
type  of  confluent  lobular  pneumonia  with  extensive  puru- 
lent bronchitis,  intense  cyanosis,  and  appearance  of  suf- 
focation, with  which  pneumococci,  in  this  case  Pneumococ- 
cus  I  Wand  B.  influenzae  are  commonly  associated.  Case.")!) 
is  illustrative  of  the  small  group  of  bronchopneumonias 
following  influenza  which  die,  often  unexpectedly,  after  a 
long-  drawn  out  course,  in  this  instance  three  weeks  after 
onset.  Examination  of  the  sputum  at  the  time  the  pneu- 
monia began,  showed  Pneumoeoccus  Type  IV  and  B.  in- 
fluenzae. At  necropsy  there  was  a  lobular  pneumonia  with 
clustered  small  abscesses,  probably  due  to  a  superimposed 
infection  with  S.  aureus.  'There  was  a  well-developed  bron- 
chiectasis in  the  left  lower  lobe.  Cultures  taken  at  autopsy 
showed  a  sterile  heart's  blood,  which  is  not  infrequently 
the  case  in  cases  of  pneumoeoccus  lobular  pneumonia  after 
influenza.  Cultures  from  the  consolidated  portions  of  the 
iung  showed  no  growth,  the  pneumoeoccus  having  disap- 
peared as  might  be  expected  from  the  duration  of  the  case. 
B.  influenzae  together  with  staphylococci  were  found  in  the 
bronchi.  In  Cases  50  and  56  a  second  attack  of  pneumonia 
caused  by  a  different  type  of  pneumoeoccus  from  that  re- 
sponsible for  the  first  attack  occurred,  the  second  attack  in 
both  instances  being  due  to  contact  infection  with  Pneumo- 
eoccus Type  II  from  a  patient  in  a  neighboring  bed  suffer- 
ing with  Pneumoeoccus  Type  IT  pneumonia.  Both  cases 
showed  at  necropsy  the  type  of  confluent  lobular  pneumonia 
so  commonly  found  in  pneumoeoccus  pneumonias  following 
influenza.  Case  107  illustrates  well  the  extent  to  which 
mixed  infections  may  occur,  especially  when  cases  are 
treated  in  crowded  hospital  wards.  The  sputum  at  time 
of  onset  showed  Pneumoeoccus  IV  in  abundance  and  a  few 
staphylococci.     At  necropsy  there  was  a  confluent  lobular 


CLTNTCAL  FEATURES  AND  BACTERIOLOGY  OF   INFLUENZA        69 


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70        PNEUMONIAS  A\H   1X1  SECTIONS  OF   RESPIRATOR?  TRACT 

pneumonia  with  clustered  abscesses,  purulenl  bronchitis, 
and  bronchiectasis  in  the  lefl  lower  lobe  The  heart's 
blood  was  sterile,  the  lungs  showed  Pneumococcus  Type  1 1 1 
and  staphylococci.  B.  influenzae  was  nol  Pound,  but  through 
oversighl  no  cultures  were  taken  from  the  bronchi.  Cases 
!'i'.  99,  L02,  and  L04  arc  all  examples  of  superimposed  hemo- 
lytic streptococcus  infection  occurring  in  the  presence  of  a 
Pneumococcus  Type  IV  pneumonia,  with  the  picture  of  in- 
terstitial suppuration,  abscess  formation,  and  empyema 
due  to  S.  hemolyticus  on  the  background  of  a  pneumococcus 
lobular  pneumonia  found  at  necropsy.  All  showed  abun- 
dant pneumococci  and  B.  influenzas  in  the  sputum  and  were 
free  from  hemolytic  streptococci  at  time  of  onset  of  pneu- 
monia, except  Case  92  which  showed  2  colonies  of  S.  hemo- 
lyticus in  the  first  sputum  culture  made.  At  time  of  death 
the  pneumococci  had  disappeared  in  all  cases  and  were  re- 
place.I  by  hemolytic  streptococci. 

The  eases  cited  in  the  preceding  paragraph  are  illustra- 
tive examples  from  a  series  of  over  250  necropsies  which 
are  described  in  another  section  of  this  report.  They  serve 
to  indicate  clearly  the  extent  to  which  mixed  and  superim- 
posed infections  of  the  lungs  may  occur  in  pneumonia 
following  influenza  and  leave  little  doubt  that  a  considerable 
proportion  of  the  deaths  from  influenzal  pneumonia  are 
clue  to  this  circumstance. 

Hemolytic  Streptococcus  Pneumonia  Following-  Influenza 

But  4  cases  of  hemolytic  streptococcus  pneumonia  di- 
rectly following  influenza  without  an  intervening  pneumo- 
coccus infection  of  the  lungs  occurred  in  the  group  of  cases 
studied  clinically.  Superimposed  infection  with  S.  hemo- 
lyticus, however,  occurred  not  infrequently  during  the 
course  of  pneumococcus  pneumonia  following  influenza,  as 
has  been  stated  above.  This  occurred  3  times  in  lobar 
pneumonia  and  10  times  in  bronchopneumonia,  with  fatal 
outcome  in  all  but  1  case. 


CLINICAL  FEATURES  AN' I)   BACTEEIOLOGY   OF   I  X  FL1  'EN'ZA        71 

Bacteriology. — Bacteriologies  examination  of  the  sputum 
in  the  4  cases  of  streptococcus  pneumonia  directly  follow- 
ing influenza  showed  S.  hemolyticus  present  in  abundance. 
B.  influenza  was  also  present  in  largo  numbers  in  3  eases, 
but  was  not  found  in  the  fourth.  In  1  ease  a  Gram-nega- 
tive micrococcus  resembling  M.  catarrhalis  was  also  pres- 
ent in  large  numbers  in  the  sputum.  Pneumococci  were 
not  found  either  by  direct  culture  on  blood  agar  plates  or 
by  inoculation  of  the  sputum  intraperitoneally  in  white 
mice. 

In  the  13  cases  of  superimposed  hemolytic  streptococcus 
infection  occurring  during  the  course  of  pneumococcus 
pneumonia,  bacteriologic  examination  of  the  sputum  by  di- 
rect culture  and  by  mouse  inoculation  shortly  after  onset 
of  the  pneumonia  showed  Pneumococci  (atypical  II  once, 
Type  III  once,  Group  IV  eleven  times)  B.  influenzae 
present  in  large  numbers,  and  no  hemolytic  streptococci  ex- 
cept in  4  instances  in  which  a  very  few  organisms  were  pres- 
ent. Subsequent  invasion  of  the  lower  respiratory  tract  by 
S.  hemolyticus  was  shown  to  occur  by  means  of  cultures  of 
empyema  fluids  or  by  cultures  made  at  necropsy. 

Clinical  Features. — The  4  cases  of  hemolytic  streptococ- 
cus pneumonia  following  influenza  that  occurred  in  this 
series  resembled  in  all  respects  the  secondary  streptococcus 
pneumonias  of  the  winter  and  spring  of  1918  and  presented 
no  features  requiring  special  comment.  The  onset  re- 
sembled that  of  pneumococcus  bronchopneumonia,  the 
disease  appearing  to  develop  as  a  continuation  of  the  pre- 
ceding influenza.  The  sputum  was  profuse  and  muco- 
purulent in  3  cases,  mucoid  and  bloody  in  the  other.  Two 
cases  ran  a  severe  and  rapid  course  with  the  development 
of  empyema  early  in  the  disease  and  fatal  outcome.  The 
other  2  cases  ran  only  moderately  severe  courses  without 
developing  empyema  and  recovered  by  lysis  in  twenty  and 
fifteen  days,  respectively,  after  the  onset  of  influenza. 
Clinical  differentiation  between  streptococcus  and  pneumo- 


coccus  bronchopneumonia  following  Influenza  did  not  seem 
possible  without  bacteriologic  examination  of  the  sputum 
excepl  in  those  cases  of  the  streptococcus  group  which  de- 
veloped an  extensive  pleural  effusion  early  in  the  disease. 
The  advent  of  superimposed  hemolytic  streptococcus  in- 
fection of  the  lower  respiratory  trad  during  the  course  of 
pneumococcus  pneumonia  following  influenza  presented  no 
clinical  features  tliat  made  diagnosis  certain  without  bac- 
teriologic examination.  The  sudden  occurrence  of  a  pleu- 
ral exudate  during  the  course  of  the  disease  seemed  of  par- 
ticular significance,  especially  since  empyema  in  the  bron- 
chopneumonias following  influenza  was  exceedingly  rare 
in  the  absence  of  hemolytic  streptococcus  infection.  Other 
suggestive  symptoms  were  a  chill  during  the  course  of  the 
disease,  a  sudden  turn  for  the  worse  in  cases  apparently 
doing  well,  or  the  development  of  a  cherry  red  cyanosis. 
None  of  these1  features,  however,  was  sufficiently  constant 
or  distinctive  of  streptococcus  invasion  to  he  depended  upon 
and  when  they  occurred,  were  merely  indications  for  fur- 
ther bacteriologic  examination. 

Bacillus  Influenzae  Pneumonia  Following'  Influenza 

Bacteriologic  evidence  that  cases  of  pneumonia  following 

influenza  might  be  due  to  B.  influenza1  alone  was  very 
meager  in  the  group  of  cases  studied  clinically  at  Camp 
Pike;  in  fact,  no  convincing  evidence  was  obtained  that 
such  cases  occurred.  In  one  case  B.  influenzae  alone  was 
found  in  the  sputum  coughed  from  the  deeper  air  passages, 
and  in  another  case  B.  influenzae  with  a  few  colonies  of  S. 
v  in  dans  was  found.  Both  were  cases  of  bronchopneu- 
monia, mild  in  character,  and  recovered  promptly.  They 
presented  no  clinical  features  by  which  they  could  he  dis- 
tinguished from  cases  of  pneumococcus  bronchopneumonia. 
It  has  been  previously  stated  that  B.  influenzae  was  found 
in  all  early  uncomplicated  cases  of  influenza  somewhere 
in  the  respiratory  trad;  that  it  was  present  together  with 


CLINICAL  FEATURES  AND   BACTERIOLOGY   OK   I  N  KLI  'EX/A        (■> 

other  organisms,  notably  pneumococcus  in  the  sputum  from 
cases  of  purulent  bronchitis  following  influenza;  and  that 
it  was  found  in  the  sputum  coughed  from  the  lung  in  ap- 
proximately 80  per  cent  of  cases  of  pneumonia  compli- 
cating influenza.  In  35  cases  it  was  very  abundant,  often 
being  the  predominating  organism.  In  all  these  cases, 
however,  pneumococci  or  hemolytic  streptococci  were  also 
present  in  considerable  numbers  at  the  time  of  onset  of  the 
pneumonia.  It  is  impossible  to  say  merely  from  the  clin- 
ical and  bacteriologic  data  under  consideration  what  part 
B.  influenza?  played  in  the  development  of  the  actual  pneu- 
monia in  these  cases.  Discussion  of  this  subject  is  there- 
fore reserved  for  the  section  of  this  report  dealing  with  the 
pathology  and  bacteriology  of  pneumonia  following  in- 
fluenza, 

Summary 

Influenza  as  observed  at  Camp  Pike  presented  itself 
as  a  highly  contagious  infectious  disease,  the  principal 
clinical  manifestations  of  which  were,  sudden  onset  with 
high  fever,  profound  prostration  with  severe  aching  pains 
in  the  head,  back  and  extremities,  erythema  of  the  face, 
neck  and  upper  chest  with  injection  of  the  conjunctivae, 
and  a  rapidly  progressive  attack  upon  the  mucous  mem- 
branes of  the  respiratory  tract  as  evidenced  by  coryza, 
pharyngitis,  tracheitis  and  bronchitis  with  their  accom- 
panying symptoms.  In  the  majority  of  cases  it  ran  a  short 
self -limited  course,  rarely  of  more  than  four  days'  dura- 
tion, and  was  never  fatal  in  the  absence  of  a  complicating 
pneumonia. 

Bacteriologic  examination  in  early  uncomplicated  cases 
of  the  disease  showed  the  B.  influenza?  of  Pfeiffer  to  be 
present  in  all  cases,  often  in  predominating  numbers.  It 
was  found  more  abundantly  present  during  the  acute  stage 
of  the  disease  than  during  convalescence  in  uncomplicated 
cases.  No  other  organisms  of  significance  were  encountered 
by  the  methods  employed. 


i4         PNEUMONIAS  AND   [NFECTIONS  OF   RESP1  RAT(  >i;  V  TRACT 

Purulent  bronchitis  of  varying  extenl  developed  in  ap- 
proximately 35  per  cenl  of  the  eases  and  often  prolonged 
the  course  of  the  illness  to  a  considerable  extent.  Bacte- 
riologic  studies  showed  thai  it  was  invariably  associated 
with  a  mixed  infection  of  the  bronchi  with  B.  influenzae  and 
other  bacteria,  in  most  instances  the  pneumococcus,  and  in- 
dicated that  it  should  be  regarded  as  a  complication  rather 
than  as  an  essential  part  of  influenza.  Its  clinical  features 
consisted  of  a  mild  febrile  reaction,  Frequent  cough  with 
the  raising  of  considerable  amounts  of  purulent  sputum, 
and  the  physical  signs  of  a  more  or  less  diffuse  bronchitis. 
It  led  to  a  varying  degree  of  bronchiectasis  in  at  least  some 
instances. 

Pneumonia  complicating  influenza  presented  a  very  di- 
versified picture  and  appeared  to  have  only  one  constant 
character,  namely,  that  influenza  was  the  predisposing 
cause.  It  may  be  best  classified  on  an  etiologic  basis  since 
the  clinical  features  to  some  extent  and  the  pathology  to  a 
much  greater  extent  depended  upon  the  infecting  bacteria 
in  a  given  case. 

Bacteriologic  examination  showed  that  a  very  large  pro- 
portion of  the  cases  was  due  to  infection  with  the  different 
immunologic  types  of  pneumococci  or  to  a  mixed  infection 
with  B.  influenza*  and  pneumococci.  The  types  of  pneumo- 
cocci commonly  found  in  normal  mouths,  namely,  II  atypi- 
cal, III,  and  IV,  comprised  approximately  88  per  cent  of 
these,  the  highly  parasitic  Pneumococci  Types  I  and  II, 
but  12  per  cent.  A  small  number  of  cases  were  due  to 
hemolytic  streptococci  or  to  mixed  infection  with  B.  influ- 
enza? and  S.  hemolyticus.  No  certain  evidence  was  obtained 
that  pneumonia  was  due  to  B.  influenza?  alone.  This  or- 
ganism was  present  in  varying  numbers,  however,  in 
approximately  80  per  cent  of  the  sputums  examined,  and 
it  seems  fairly  certain  that  it  must  have  played  at  least 
a  part  in  the  development  of  the  pneumonia  in  many  of 
the  cases  in  which  it  was  found.     Superimposed  infections 


CLINICAL  FEATURES  AND   BACTERIOLOGY  OE   I  X  FL1  'KX/A       75 

with  other  typos  of  pneumococci  than  those  primarily  re- 
sponsible for  the  development  of  pneumonia,  with  hemo- 
lytic streptococci  and  with  Staphylococcus  aureus  occurred 
frequently  in  cases  of  pneumococcus  or  mixed  pneumococcus 
and  B.  influenzae  pneumonia  and  undoubtedly  conl  ributed  to 
a  considerable  extent  in  increasing  the  number  of  deaths. 

Three  clinical  types  of  pneumococcus  pneumonia  follow- 
ing influenza  occurred:  lobar  pneumonia,  lobar  pneumonia 
with  purulent  bronchitis,  and  bronchopneumonia.  Lobar 
pneumonia  was  usually  sudden  in  onset  and  ran  the  char- 
acteristic course  of  the  primary  disease.  Lobar  pneumonia 
with  purulent  bronchitis  similarly  ran  the  characteristic 
course  of  the  primary  disease  but  presented  the  unusual 
picture  of  lobar  pneumonia  with  mucopurulent  rather  than 
rusty,  tenacious  sputum  and  numerous  moist  rales  through- 
out the  unconsolidated  portions  of  the  lungs.  The  cases 
of  bronchopneumonia  ran  a  very  variable  course  from  mild 
cases  of  a  few  days '  duration  and  meager  signs  of  consoli- 
dation to  rapidly  progressive  cases  with  signs  of  extensive 
pulmonary  involvement.  Purulent  bronchitis  was  very 
frequently  associated  with  bronchopneumonia. 

Hemolytic  streptococcus  pneumonia  following  influenza 
presented  the  clinical  picture  of  bronchopneumonia  and  was 
not  readily  distinguished  on  clinical  grounds  from  pneu- 
mococcus bronchopneumonia  except  in  those  cases  which 
developed  a  pleural  exudate  early  in  the  disease.  The  ad- 
vent of  tertiary  infection  of  the  lower  respiratory  tract  with 
hemolytic  streptococci  in  cases  of  secondary  pneumococcus 
pneumonia  presented  no  symptoms  sufficiently  constant  or 
certain  to  make  clinical  diagnosis  easy.  The  development 
of  empyema  in  pneumococcus  bronchopneumonia  usually 
meant  streptococcus  infection. 

Pure  B.  influenzae  pneumonia,  if  such  cases  existed,  pre- 
sented no  diagnostic  features  by  which  it  could  be  distin- 
guished from  pneumococcus  bronchopneumonia  following 
influenza.     It  was  impossible  to  determine  on  clinical  and 


.1)        PNEUMONIAS  AX!)   1  X  FECTN  »XS  OF   RESPIRATORS  TRACT 

bacteriologic  grounds  alone  what  part  the  prevalent  in- 
fluenza bacilli  played  in  the  causation  of  the  actual  pneu- 
monia. 

Discussion 

That  wide  variations  in  the  conception  of  influenza  have 
arisen  during  the  recent  pandemic,  even  a  hasty  review  of 
the  literature  makes  clear.  In  its  essence  this  divergence 
of  opinion  seems  to  depend  upon  whether  pneumonia  is 
considered  an  essential  pari  of  influenza  or  a  complica- 
tion due  either  to  the  primary  cause  of  influenza  or  to 
secondary  infection.  One  extreme  is  expressed  by  Dunn8 
who  says  "the  so-called  complication  is  the  disease,"  the 
other  by  Fantus4  who  finds  influenza  a  relatively  mild 
disease  with  pneumonia  a  relatively  infrequent  and  largely 
preventable  complication. 

A  similar  divergence  of  opinion  prevails  with  respect  to 
the  bacteriology  of  influenza.  There  is  fairly  general 
agreement  that  the  members  of  the  pneumococcus  and 
streptococcus  groups  and  to  a  less  extent  other  organisms 
are  responsible  for  a  large  proportion  of  the  secondary 
pneumonias,  and  but  few  observers  hold  that  they  possess 
any  etiologic  relationship  to  influenza.  No  such  uniform- 
ity of  opinion  exists,  however,  with  respect  to  the  relation 
of  B.  influenzae  to  influenza  and  to  the  complicating  pneu- 
monia. By  some  it  is  considered  the  primary  cause  of 
influenza,  by  others  it  is  regarded  as  a  secondary  invader 
responsible  for  a  certain  proportion  of  the  secondary 
pneumonias,  and  by  still  others  it  is  not  considered  to  bear 
any  relation  either  to  influenza  or  its  complications. 

A  limited  number  of  references  to  the  extensive  litera- 
ture of  the  recent  pandemic  will  amply  serve  to  illustrate 
the  various  points  of  view  that  have  developed. 

Keegan5  regards  pneumonia  as  a  complication  and  con- 
siders that  B.  influenza1,  the  probable  cause  of  influenza,  is 


3I)unn:  Jour.  Am.  Med.  Assn.,  1918,  lxxi,  2128. 
«Fantus:  Jour.  Am.  Med.  Assn.,  1918.  lxxi,  1736. 
5Keegan:     Jour.   Am.   Med.   Assn..   191S,  lx.xi,    1CS1. 


CLINICAL  FEATURES  AND  BACTERIOLOGY  OF   [NFLTJENZA       77 

the  primary  cause  of  the  pneumonia  which  may  or  may  not 
be  still  further  complicated  by  pneumococcus  or  si  reptococ- 
cus  infection  as  a  terminal  event.  Christian0  states  thai 
epidemic  influenza  causes  a  clinically  demonstrable  bron- 
chitis and  bronchopneumonia  in  the  larger  proportion  of 
cases,  and  lays  particular  emphasis  upon  the  fact  that  it 
is  quite  incorrect  to  consider  fatalities  in  the  epidemic  as 
due  to  influenza  uncomplicated  by  bronchopneumonia. 
Blanton  and  Irons7  speak  of  influenza  as  an  "antecedent 
respiratory  infection"  of  undetermined  etiology,  and  be- 
lieve that  pneumonia  when  it  occurs  is  due  to  autogenous 
infection  by  a  variety  of  secondary  invaders,  principally 
of  the  pneumococcus  and  streptococcus  groups.  Hall, 
Stone,  and  Simpson8  regard  pneumonia  strictly  as  a  com- 
plication and  quite  distinct  from  influenza  itself.  Synnott 
and  Clark9  believe  that  the  infection  is  characterized  by  a 
progressive  intense  exudative  inflammation  of  the  respira- 
tory tract  often  terminating  in  an  aspiration  pneumonia 
with  a  variety  of  conditions  found  at  autopsy  and  a  mul- 
tiplicity of  secondary  organisms  responsible  for  the  fatal 
termination.  B.  influenzae  was  usually  found  but  always 
with  other  organisms.  Friedlander  and  his  collaborators10 
speak  of  a  fulminating  fatal  type  of  influenza  with  acute 
inflammatory  pulmonary  edema,  but  regard  true  broncho- 
pneumonia as  secondary,  due  to  infection  with  pneumococ- 
cus or  S.  hemolyticus.  B.  influenzas  was  not  found  more 
frequently  than  under  normal  conditions.  Brem11  and  his 
collaborators  present  a  clear  cut  clinical  picture  both  of 
influenza  and  the  secondary  pneumonia  to  which  it  predis- 
poses, regarding  the  latter  as  definitely  due  to  secondary 
infection  with  pneumococcus,  streptococcus  or  B.  influenzae, 
the  virus  of  influenza  being  unknown.     Ely12  and  his  col- 


°Christian:     Jour.   Am.   Med.   Assn.,    1918,   lxxi,    1565. 

7Blanton  and  Irons:       Jour.   Am.   Med.   Assn.,    1918,  lxxi.    19S8. 

8Hal1,    Stone   and   Simpson.,   Jour.   Am.   Med.   Assn.,    1918,   lxxi,    19S6. 

;,Synnott  and    Clark:     Jour.    Am.    Med.   Assn.,    1918,   lxxi,    1816. 

10Friedlander,    McCord,    Sladen    and    Wheeler:     Tour.    Am.    Med.    Assn.,    191S.    lxxi,    1652. 

"Brem,  Boiling  and  Casper:     Jour.  Am.  Med.,  Assn.,   1918,  lxxi,  213S. 

12Ely,   Lloyd,    Hitchcock,   and   Nickson:     Jour.    Am.    Med.   Assn.,    1919,    lxxii,    24. 


(8         PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATOR?  TRACT 

laborators  make  no  distinction  between  influenza  and  pneu- 
monia, and  apparently  consider  the  epidemic  due  to  a  hemo- 
lytic streptococcus  of  indefinite  and  inconstant  characters. 
The  Camp  Lewis  Pneumonia  Unit13  slates  "the  process 
[influenza],  whether  mild  or  severe,  is  etiologically  and 
pathologically  the  same;  *  :  V  B.  influenza1  was  not 
found.  In  a  report  of  The  American  Public  Health  Asso- 
ciation1' it  is  stated  that  deaths  resulting  from  influenza 
are  commonly  due  to  pneumonias  resulting  from  an  in- 
vasion of  the  lungs  by  one  or  more  forms  of  streptococci, 
by  one  or  more  forms  of  pneumoeoeci,  or  by  the  so-called 
influenza  bacillus.  This  invasion  is  apparently  secondary 
to  the  initial  attack.  Wolbach15  found  B.  influenzae  in  a 
high  proportion  of  cases,  not  infrequently  in  pure  culture 
in  the  lung,  and  believes  that  there  is  a  true  influenzal  pneu- 
monia whether  B.  influenzae  is  the  cause  of  the  primary  dis- 
ease or  not.  Spooner,  Scott  and  Heath16  isolated  B.  in- 
fluenzae in  a  high  percentage  of  cases  and  consider  it 
reasonable  to  suppose  that  it  was  the  prime  factor  in  the 
epidemic.  Kinsella17  found  B.  influenzae  infrequently  and 
regards  it  as  a  secondary  invader.  MacCallumls  regards 
B.  influenzae  as  a  secondary  invader  and  believes  that  it  is 
responsible  for  a  form  of  purulent  bronchitis  and  broncho- 
pneumonia following  certain  cases  of  influenza.  Pritchett 
and  Stillman10  found  B.  influenzae  in  93  per  cent  of  cases  of 
influenza  and  bronchopneumonia.  Hirsch  and  McKinney20 
state  that  B.  influenza^  played  no  role  in  the  epidemic  at 
Camp  Grant  and  apparently  consider  it  due  to  a  specially 
virulent  pneumococcus. 

Xo  further  references  to  the  extensive  literature  of  the 
recent  pandemic  seem  necessary,  since  those  cited  above 
serve  to   illustrate  the  various  points  of  view  that  exist. 


"Camp  Lewis   Pneumonia   Unit:     Jour.    Am.    Med.   Assn.,    1919,    lxxii,    268. 

"Jour.   Am.    Med.   Assn.,    1918,   lxxi,   2068. 

'•'•Wolbach :     Hull.    Johns   Hopkins   IIosp.,    1919,   xxx,    104. 

"Spooner,   Scott  and   Heath:     Jour.   Am.   Med.   Assn.,    1919,   lxxii,    155. 

"Kinsella:     Jour.   Am.   Med.   Assn.,    1919,   lxxii,   717. 

"MacCalluin:     Jour.    Am.    Med.   Assn.,    1919,   lxxii,    720. 

luPritchett   and    Stillman:     Jour.    F.xper.   Med.,    1919,    xxix,   259. 

-"Ilirsch   and   McKinney:     Jour.  Am.   .Mid.   Assn.,   1918,   lxxi,    1735. 


CLINICAL  FEATURES  AND  BACTERIOLOGY  OF   IM'IJ'KXZA        79 

A  similar  diversity  of  opinion  may  be  found  in  the  reports 
from  foreign  sources. 

It  would  appear  that  much  of  the  divergence  of  opinion 
that  has  been  formed  has  depended  to  a  considerable  ox- 
tent  upon  the  conditions  under  which  cases  have  been  ob- 
served. This  is  clearly  brought  out  by  contrasting  the 
experience  of  Fantus4  dealing  with  private  cases  in  civilian 
practice,  where  pneumonia  was  relatively  uncommon,  with 
that  of  others  dealing  only  with  cases  in  large  hospitals, 
where  those  admitted  have  been  in  large  part  selected  se- 
riously ill  patients  with  a  high  incidence  of  pneumonia,  the 
milder  cases  comprising  from  60  to  90  per  cent  of  those 
attacked  by  influenza  never  reaching  the  hospital.  Varia- 
tions in  opinion  with  respect  to  the  bacteriology  of  the 
epidemic,  especially  in  regard  to  B.  influenzae,  would  appear 
to  be  due  for  the  most  part  to  differences  in  bacteriologic 
technic,  in  some  degree  to  differences  in  interpretation. 
Accumulating  evidence  can  leave  little  doubt  that  B.  in- 
fluenzas was  at  least  extraordinarily  and  universally  preva- 
lent throughout  the  period  of  the  epidemic  and  thereafter, 
and  that  earlier  reports  of  failure  to  find  it  were  due  to  the 
use  of  methods  unsuitable  for  its  detection  and  isolation. 

The  opportunit}r  afforded  the  commission  at  Camp  Pike 
to  devote  their  full  time  to  a  systematic  and  correlated 
group  study  of  the  epidemic  simultaneously  from  many 
aspects  throughout  its  whole  course  made  it  apparent  that 
influenza  per  se  is  in  the  large  majority  of  instances,  in 
spite  of  the  initial  picture  of  profound  prostration,  a  rela- 
tively mild  disease  which  tends  to  rapid  spontaneous  re- 
covery. This  opinion  is  supported  by  the  fact  that  the 
disease  during  the  first  waves  of  the  epidemic  in  this  coun- 
try, which  it  is  now  recognized  occurred  pretty  generally 
in  the  army  camps  during  the  spring  of  1918,  was  so  mild 
that  it  attracted  only  passing  attention,  since  the  disease  ' 
at  that  time  was  not  sufficiently  virulent  to  predispose  to 
any  alarming  amount  of  pneumonia.     AVith  the  return  of 


SO        PNEUMONIAS  A.ND   [NFECTIONS  <>!'   RESPIRATOR'S  TRACT 

the  epidemic  in  the  late  summer  and  early  fall,  however, 
the  disease  had  attained  such  a  high  degree  of  virulence 
thai  it  predisposed  to  an  appalling  amount  of  severe  and 

often  rapidly  fatal  pneumonia,  which  often  detracted  at- 
tention from  the  real  nature  of  the  preceding  disease. 
Vet  even  during  the  fall  epidemic  Prom  60  to  90  per  cent 
i^\'  the  cases  of  influenza  proceeded  to  rapid  recovery  with- 
out developing  complications.  On  this  ground  alone  it 
would  seem  only  logical  to  regard  pneumonia  strictly  as  a 
complication  of  influenza  rather  than  as  an  essential  part 
of  the  disease,  irrespective  of  whether  the  pneumonia  may 
be  caused  by  the  primary  cause  of  influenza  or  not.  The 
complexity  of  the  clinical  features,  the  bacteriology  and 
pathology  of  the  pneumonias  following  influenza  lend  fur- 
ther support  to  this  opinion. 

It  seems  better,  therefore,  to  consider  influenza  first  as 
a  disease  by  itself  and  subsequently  to  take  up  the  question 
of  pneumonia  and  the  relation  of  influenza  to  it. 

The  most  striking  clinical  features  of  influenza  are  its 
epidemic  character,  its  involvement  of  the  respiratory 
tract,  its  extremely  prostrating  effect,  and  the  often  sur- 
prising- rapidity  with  which  the  individual  cures  himself. 
These  features  strongly  suggest  that  the  etiologic  agent  of 
the  disease  is  an  organism  subject  to  rapid  changes  in  vir- 
ulence; that  it  is  confined  to  the  respiratory  tract  where  it 
produces  a  superficial  inflammatory  reaction  giving  rise  to 
the  characteristic  symptoms  of  coryza,  pharyngitis  and 
tracheitis;  that  it  elaborates  a  poison,  possibly  a  true  toxin, 
readily  absorbed  by  the  lymphatics,  the  effect  of  which  is 
manifested  in  the  profound  prostration,  severe  aching 
pains,  erythema,  and  leucopenia;  and  that  it  may  either 
disappear  promptly  from  the  respiratory  mucous  mem- 
brane at  time  of  recovery  or  may  persist,  leading  a  rela- 
tively saprophytic  existence  for  an  indefinite  period  of 
time,  being  no  longer  harmful  to  the  individual,  at  least 
more  than  locally,  because  of  an  acquired  immunity*.     Put* 


CLINICAL  FEATURES  AND   BACTERIOLOGY  03?   IN  I-'Ll'KXZA       81 

thermore,  in  our  opinion,  the  very  brief  incubation  period 

suggests  that  the  disease  is  bacterial  in  origin,  rather  than 
that  it  is  analogous  to  the  exanthemata,  the  majority  of 
which  present  a  comparatively  long,  fairly  constant,  incu- 
bation period. 

B.  influenzae  has  characteristics  in  accord  with  the  clinical 
features  of  influenza.  It  is  an  organism  of  very  labile  viru- 
lence; it  is  always  present  in  our  experience  on  the  mucous 
membranes  of  the  respiratory  tract  in  early  uncomplicated 
cases  of  influenza,  often  in  overwhelming  numbers ;  in  only 
very  exceptional  instances,  in  adults  at  least,  does  it  invade 
the  body  producing  a  general  infection,  as  the  numerous 
reports  of  negative  blood  cultures  testify ;  recent  investiga- 
tions by  Parker21  and  others  indicate  that  it  is  capable  of 
producing  a  toxin  quickly  fatal  for  rabbits ;  it  is  predomi- 
nantly present  in  the  respiratory  tract  during  the  active 
stage  of  the  disease  and  disappears  in  a  considerable  pro- 
portion of  cases  at  time  of  recovery,  while  in  others,  more 
particularly  those  that  develop  an  extensive  secondary 
bronchitis  and  bronchiectasis  it  may  persist  for  an  in- 
definite period  of  time. 

It  is,  of  course,  fully  appreciated  that  the  foregoing  is 
in  the  main  merely  argumentative  reasoning  and  it  is  put 
forth  only  to  suggest  that  B.  influenzae  merits  a  much  closer 
scrutiny  with  respect  to  its  etiologic  relationship  to  influ- 
enza than  the  trend  of  present  opinion  has  awarded  it. 

Although  there  remains  some  difference  of  opinion  as  to 
the  relation  of  influenza  to  pneumonia,  the  majority  of  ob- 
servers concur  in  regarding  pneumonia  as  a  complication 
and  this  would  seem  to  be  the  only  logical  interpretation  of 
the  facts  available.  The  same  may  be  said  with  respect  to 
purulent  bronchitis  and  bronchiectasis.  It  is  of  consider- 
able significance  in  this  connection  that  pneumonia  follow- 
ing influenza  presents  no  uniform  clinical  picture,  no  uni- 
form bacteriology  and  no  uniform  pathology.     "Whether  the 

21Parker:     Jour.  Am.   Med.  Assn.,    1919,   lxxii,   476. 


^L1        PNEUMONIAS  AND  IX  V ECTIONS  OF  RESPIRATORS  TRACT 

predisposition  of  patients  with  influenza  to  contract  pneu- 
monia is  preponderantly  due  to  lowering  of  general  resist- 
ance to  infection  by  the  extremely  prostrating  effect  of  the 

disease  and  the  inhibition  of  leucocytic  defense,  or  to  a  de- 
struction of  local  resistance  againsl  bacterial  invasion  by 
reason  of  profound  injury  to  the  bronchia]  mucosa,  or  to  a 
combination  of  both  factors,  is  difficult  to  say.  It  seems 
most  probable  that  both  are  concerned.  At  any  rate  it 
seems  clear  that  in  the  presence  of  influenza  a  considerable 
variety  of  organisms  which  under  ordinary  conditions  do 
not  find  lodgement  in  the  lungs  are  able  to  gain  access  to 
the  lower  respiratory  tract  and  produce  pneumonia. 


CHAPTER  III 

SECONDARY  INFECTION  IN  THE  WARD  TREAT- 
MENT OF  INFLUENZA  AND  PNEUMONIA 

Eugene  L.  Opie,  M.D. ;  Francis  G.  Blake,  M.D. ;  James  C. 
Small,  M.D. ;  and  Thomas  M.  Rivers,  M.D. 

One  of  the  most  pressing  problems  that  presented  itself 
in  the  care  of  influenza  and  pneumonia  patients  in  the  army 
cantonments  during  the  recent  epidemic  was  the  danger  of 
secondary  contact  infection  because  of  the  overcrowding  of 
the  base  hospitals,  nearly  all  of  which  were  taxed  far  be- 
yond the  limits  of  their  capacity.  That  this  danger  was 
very  real  was  fully  demonstrated  by  certain  studies  in  ward 
infection  that  this  commission  was  able  to  make  at  Camp 
Pike1.  It  is  the  purpose  of  the  present  section  of  the  re- 
port to  present  these  studies  and  to  discuss  the  means 
whereby  this  danger  may  be  most  successfully  met. 

It  is  perhaps  well,  first  to  define  exactly  what  is  meant 
by  secondary  contact  infection  in  influenza  and  pneumonia. 
In  our  experience  at  Camp  Pike  it  was  found  that  a  very 
large  percentage  of  the  pneumonias  following  influenza 
were  accompanied  by  secondary  infection  with  pneumococ- 
cus,  some  few  being  caused  by  hemolytic  streptococcus. 
The  types  of  pneumococcus  encountered  were  almost  en- 
tirely those  that  are  found  normally  in  the  mouths  of 
healthy  men,  approximately  85  per  cent  being  Types  II 
atypical,  III,  and  IV.  It  has  been  generally  accepted  that 
infection  with  these  types  of  pneumococci  is  usually  autog- 
enous— that  is,  that  under  the  proper  conditions  of  low- 
ered resistance  an  individual  becomes  infected  with  the 
pneumococcus  that  he  carries  in  his  own  mouth.    Many  ob- 


10pie,   Freeman,   Blake,    Small   and   Rivers:     Jour.    Am.    Med.    Assn.,    1919,    Ixxii,    556. 

S3 


^4        PNEUMONIAS  AND  [NFECTIONS  OF  RESPIRATORY  TRACT 

servations  made  during  the  course  of  the  present  work 
have  suggested  thai  this  is  probably  nol  so  in  many  in- 
stances and  thai  the  influenza  patienl  may  qo1  be  so  much 
in  daimor  Prom  the  pneumococcus  thai  be  normally  carries 
in  his  own  mouth  as  he  is  from  that  carried  by  his  neighbor, 
in  other  words,  he  is  in  danger  from  contact  infection.  The 
same  considerations  hold  true  with  respect  to  hemolytic 
streptococcus  infection.  Secondary  contact  infection  in 
eases  of  already  existing  pneumonia  following  influenza 
were  round  to  occur  frequently.  These  were  for  the  most 
pail  caused  by  hemolytic  streptococcus  infection  superim- 
posed upon  a  pneumococcus  pneumonia.  Many  instances 
of  double  pnonmococcns  infection,  however,  either  coinci- 
dent with  or  following  one  another  were  encountered. 

Secondary  Infection  with  S.  Hemolyticus  in  Pneumonia 
Pneumonia  caused  by  streptococci  was  repeatedly  ob- 
served2 during  the  pandemic  of  influenza  which  occurred  in 
1889-90.  With  clearer  recognition  of  the  characters  which 
distinguish  varieties  of  streptococci  several  observers  have 
shown  that  secondary  infection  with  hemolytic  streptococci 
may  occur  during  the  course  of  pneumonia  and  though  defi- 
nite evidence  lias  been  lacking  have  suggested  that  it  may 
he  acquired  within  hospital  wards.  That  a  similar  second- 
ary infection  with  S.  hemolyticus  in  pneumococcus  pneu- 
monias following  influenza  occurred  not  infrequently  at 
Camp  Pike  during  the  epidemic  was  shown  by  bacteriologic 
studies  made  during  life  and  at  autopsy  in  a  considerable 
series  of  cases.  During  the  early  days  of  the  epidemic  of 
influenza,  secondary  streptococcus  infection  was  almost 
entirely  limited  to  certain  wards  which  were  opened  for 
the  care  of  the  rapidly  increasing  number  of  patients 
with  pneumonia.  During  this  period  these  wards  were 
overcrowded,  organization  was  incomplete,  and  the  op- 
portunities   for  transfer  of   infection    from  patient   to  pa- 


-S<i    discussion  on  pages   115  to  118. 


SECONDARY    INKKCTION    IX    W'A  HI)   TKKAT.VI  10  XT 


85 


tient  .were  almost  unlimited.  The  spread  of  streptococcus 
contagion  and  its  fata]  effect  may  be  clearly  brought  owl 
by  comparison  of  these  wards  with  wards  thai  had  Long 
been  organized  for  the  care  of  patients  with  pneumonia. 

Ward  3  had  been  in  use  for  the  care  of  patients  with 
pneumonia  for  some  time  prior  to  the  outbreak  of  influenza. 
It  was  provided  with  sheet  cubicles  and  conducted  by  medi- 
cal officers,  nurses  and  enlisted  men  accustomed  to  the  care 
of  patients  with  pneumonia,  ordinary  precautions  being 
taken  against  transfer  of  infection  from  one  patient  to  an- 
other. The  data  in  Table  XVII  show  the  average  number 
of  patients  in  the  ward,  the  number  of  new  cases  of  pneu- 
monia admitted,  and  the  number  of  deaths  among  patients 
admitted  during  the  corresponding  period,  for  three  periods 
of  ten  days  each  from  September  6  to  October  5.  The 
types  of  infection  in  fatal  cases  as  determined  by  cultures 
taken  at  autopsy  are  also  shown. 


Table  XVII 
Pneumonia  in  Ward  3 


o 

m  Q 
W    «    Eh    m 

2    S     &    < 

<  CC     jvj     K, 

«   3   tj  ? 

p  §  ^ 

>   p   <i  > 

<  !z    a,   E 

18.6 
46.1 
58.6 

NUMBER   OF 

PATIENTS 

ADMITTED 

TOTAL 

DEATHS 

CULTURES  AT  AUTOPSY 

AMONG     PATIENTS 
ADMITTED    DURING 
THE     CORRESPOND- 
ING  PERIOD 

6   W 

Is 

2  p 

H    ""H 

-r      J 

s  q  5  > 

fH    H    ^    !8 
W    2    O   h 

NUMBER 

PER   CENT 

5  s  c.eh 

Sept.  6-15 

Sept.  16-25 

Sept.  26— 

Oct.  5 

11 

52 
23 

3 

16 

8 

27.2 

30.7 
34.7 

3 

13 

5 

0 

1 
1 

0 
2 
2 

During  the  period  from  September  6  to  15,  just  prior  to 
the  outbreak  of  influenza  in  epidemic  proportions,  the  ward 
had  an  average  population  of  18.6  patients.  The  total 
number  of  new  patients  admitted  was  11,  of  whom  3  died, 
a  mortality  of  27.2  per  cent.  All  these  cases  were  pneu- 
mococcus  pneumonias  as  determined  by  bacteriologic  ex- 
amination of  the  sputum  at  time  of  admission.  The  3  fatal 
cases  showed  pneumococcus  infection  at  autopsy.  During 
the  second  period,  from  September  16  to  25,  with  the  out- 


86        PNEUMONIAS  ANIi   [NFECTIONS  OF   RESPIRATOR'S  TRACT 

break  of  the  epidemic  of  influenza,  the  ward  rapidly  filled 
with  new  cases  of  pneumonia,  attaining  an  average  popula- 
tion of  46J  patients.  Of  the  52  new  cases  admitted  16 
died,  a  mortality  of  .'50.7  per  cent.  Again  all  the  cases  ad- 
mitted during  this  period  iii  which  bacteriologic  examina- 
tion (if  the  sputum  was  made,  were  found  to  lie  piienniococ- 
eus  pneumonias  with  one  exception.  This  case,  admitted 
on  September  21  and  dying  two  days  later,  had  a  hemolytic 
streptococcus  pneumonia.  Fortunately,  though  quite  by  ac- 
cident, he  was  placed  in  a  bed  at  one  end  of  the  porch  and 
no  transmission  of  streptococcus  infection  to  other  cases 
in  the  ward  took  place.  At  autopsy  13  cases  showed  pneu- 
mococcus infection;  the  foregoing  case,  hemolytic  strepto- 
coccus. During  the  third  period  from  September  2G  to 
October  5  the  ward  became  even  more  crowded,  having  an 
average  of  58.6  patients;  23  new  cases  were  admitted,  8  of 
whom  died,  a  mortality  of  34.7  per  cent.  Autopsy  showed 
that  5  of  these  were  pneumococcus  pneumonias  and  1  was 
caused  by  hemolytic  streptococcus  infection.  It  is  note- 
worthy that  the  death  rate  from  pneumonia  gradually  in- 
creased as  the  ward  became  more  and  more  crowded.  This 
may  possibly  be  attributed  in  part  to  the  increasing  severity 
of  the  pneumonia  during  the  early  days  of  the  influenza 
epidemic.  That  it  was  in  part  directly  due  to  secondary 
contact  infection  with  pneumococcus  will  be  shown  when 
the  transmission  of  pneumococcus  infection  is  discussed. 
In  spite  of  the  overcrowding-  of  the  ward  the  introduction 
of  2  cases  of  streptococcus  pneumonia  did  not  cause  an  out- 
break of  streptococcus  infection.  Whether  this  was  due 
to  precautions  taken  against  the  transfer  of  infection  or 
was  merely  a  matter  of  good  luck  is  difficult  to  say,  in  view 
of  the  fact  that  a  considerable  amount  of  transfer  of  pneu- 
mococcus infection  from  one  patient  to  another  did  occur. 

Ward  8  had  long  been  used  for  the  care  of  colored  pa- 
tients with  pneumonia.     As  in  Ward  3  cubicles  were  in  use 


SECONDARY  INFECTION    IN   WAKI)  TUKATMKNT 


87 


and  ordinary  precautions  against  the  transfer  of  infection 
were  used.     The  data  are  presented  in  Table  XVIII. 


Table  XVIII 
Pneumonia  in  Ward  8 


AVERAGE 
NUMBER    OF 
PATIENTS 
IN    WARD 

NUMBER    OF 

PATIENTS 

ADMITTED 

TOTAL 

DEATHS 

CULTURES  AT  AUTOPSY 

AMONG     PATIENTS 
ADMITTED    DURING 
THE     CORRESPOND- 
ING  PERIOD 

PNEUMO- 
COCCUS 

S.  HEMO- 
LYTICUS 

UNDETER- 
MINED 
(NO  AU- 
TOPSY ) 

NUMBER 

PER   CENT 

Sept. 

6-20 
Sept.  21 

—Oct.  5 

25.5 
46.1 

18 

59 

2 

20 

11.1 

33.9 

2 
10 

0 
1 

0 
9 

During  the  period  from  September  6  to  20,  prior  to  the 
outbreak  of  influenza  in  epidemic  proportions  among  the 
colored  troops,  the  ward  had  an  average  population  of  25.5 
patients ;  18  new  cases  of  pneumonia  were  admitted  during 
this  period,,  all  of  whom  were  pneumococcus  pneumonias 
as  determined  by  bacteriologic  examination  of  the  sputum 
at  time  of  admission  to  the  ward.  Only  2  died,  a  mortality 
of  11.1  per  cent,  autopsy  cultures  showing  pneumococcus 
in  both  cases.  All  these  patients  were  treated  on  the  porch 
of  the  ward  while  they  were  acutely  sick.  During  the  sec- 
ond period  from  September  21  to  October  5,  when  the  in- 
fluenza epidemic  was  at  its  height,  the  ward  rapidly  filled 
with  active  cases  of  pneumonia  and  became  distinctly 
crowded.  It  contained  an  average  of  46.1  patients,  but 
had  actually  reached  a  population  of  64  patients  at  the  end 
of  the  period.  Of  the  59  new  cases  admitted,  20  died,  a 
mortality  of  33.9  per  cent,  10  with  pneumococcus  pneu- 
monia, one  with  hemolytic  streptococcus  pneumonia.  In 
9  there  was  no  autopsy.  The  conditions  in  Ward  8  were 
quite  analogous  to  those  in  Ward  3.  In  spite  of  the  over- 
crowding during  the  second  period  no  outbreak  of  second- 
ary infection  with  S.  hemolyticus  occurred,  but  secondary 
pneumococcus  infection  did  occur  as  will  be  shown  below. 


^s         PNEUMONIAS  AND   [NFECTIONS  OF    RESPIRAT0R1    TRACT 

lii  contrasl  with  these  two  wards  arc  Wards  1  and  2  in 
which  widespread  secondary  contacl  infection  with  S. 
heniolyticus  took  place.  Ward  2  was  opened  September 
26,  ai  the  beginning  of  the  period  when  20  new  wards  for 
pneumonia  were  organized.  From  September  l!(>  to  Octo- 
ber 1  the  cubicle  system  was  net  in  use,  the  ward  was 
crowded,  organization  was  imperfect,  ami  few  precautions 
were  taken  to  prevent  transfer  of  infection  from  one  pa- 
tient to  another.  On  October  '2  the  cubicle  system  was 
installed  and  precautions  againsl  transfer  of  infection  were 
instituted.     The  data  are  shown  in  Table  XIX. 


Table  XIX 

I'XKI'.MOXIA   IN   W  \i:i>   - 


. 

TOTA  L 

DEATHS 

CULTURES  AT  AUTOPSY 

AMONG      PATIENTS 

o 

c 

NUMBER 
g   PATIENTS 
IN    WARD 

M  NUMBER 
°  PATIENTS 
ADMITTED 

ADMITTED    DURING 
THE     CORRESPOND- 
ING  PERIOD 

6 

p 
tn 

z, 

K 

P 

o 
o 
o 
o 

2  p 

g   _ 

w  p 

DETER- 
INED 
NO  AU- 
OPSY) 

NUMBER 

PER  CENT 

P 

Sept.  26 

Sept.  27 

27 

17  HO 

27 

67.5 

0 

23 

4 

Sept.  28 

40 

13  J 

Sept.  29 

.11 

121 

Sept.  30 

49 

1  H7 

6 

35.3 

o 

2 

0 

Oct.     1 

43 

4J 

Oct.     2 

47 

61 

Oct.     3 

42 

0  U0 

4 

40.0 

2 

1 

1 

Oct.     4 

41 

4J 

During-  the  first  three  days  40  patients  with  pneumonia 
were  admitted  to  the  ward.  Of  these  40  patients,  Ti  died, 
a  mortality  of  67.5  per  cent.  Cultures  at  autopsy  showed 
that  23  of  these  died  with  hemolytic  streptococcus  infection, 
none  of  pneumococcus  infection.  In  four  there  was  no  au- 
topsy. To  appreciate  the  full  significance  of  these  figures 
it  must  be  emphasized  that  these  patients  at  time  of  ad- 
mission to  the  ward  in  no  way  differed  from  those  admitted 
to  Ward  3  during  the  corresponding  period  and  were  not 
in  any  sense  selected  cases.  The  type  of  infection  in  9  of 
these  patients  had  been  determined  by  bacteriologic  exami- 


SECONDARY    INDUCTION    IN"    WARD  TREATMENT  89 

nation  of  tho  sputum  just  prior  to  or  immediately  after  ad- 
mission to  the  ward  before  opportunity  for  secondary  eon- 
tact  infection  in  this  ward  had  occurred.  All  9  were  shown 
to  have  pneumococcus  pneumonia  free  from  hemolytic  si  rep- 
tococci  at  that  time.  All  9  died,  7  with  secondary  strepto- 
coccus infection  as  shown  by  cultures  taken  at  autopsy,  1 
with  a  secondarily  acquired  Pneumococcus  Type  III  infec- 
tion— sputum  showed  a  Pneumococcus  Type  IV  on  admis- 
sion— and  in  1  there  was  no  autopsy.  In  view  of  the  fact 
that  bacteriologic  examination  of  the  sputum  in  cases  of 
pneumonia  following  influenza  had  shown  that  the  large 
majority  of  them  were  due  to  pneumococcus  infection,  it  is 
probable  that  most  of  the  other  cases  of  pneumonia  ad- 
mitted to  this  ward  were  pneumococcus  pneumonias  at  time 
of  admission,  and  that  they  acquired  the  streptococcus  in- 
fection after  admission. 

During  the  next  three  days  17  new  patients  were  admit- 
ted, of  whom  6  died,  a  mortality  of  35.3  per  cent.  Cultures 
at  autopsy  showed  pneumococcus  infection  in  2,  strepto- 
coccus in  2.  It  is  noteworthy  that  the  porch  was  first  put 
into  use  on  September  29.  Of  the  12  patients  admitted  on 
this  date,  8  were  treated  throughout  the  acute  stage  of  their 
illness  on  the  porch.  Of  these  8  patients  but  one  died,  of 
a  Pneumococcus  T}^pe  IV  infection  and  none  became  in- 
fected with  S.  hemolyticus.  From  October  4  to  October  6, 
10  patients  were  admitted,  of  whom  4  died.  Cultures  at 
autopsy  showed  pneumococcus  infection  in  2,  hemolytic 
streptococcus  in  1. 

The  widespread  prevalence  of  hemolytic  streptococcus 
infection  in  this  ward  as  compared  with  its  almost  entire 
absence  in  Wards  3  and  8  is  very  striking.  Cultures  made 
during  life  and  at  autopsy  have  shown  clearly  that  it  was 
due  to  rapid  spread  of  contagion  throughout  the  ward. 
The  almost  unlimited  opportunities  for  transfer  of  infection 
from  patient  to  patient,  during  the  first  six  days  the  ward 
was  in  use,  undoubtedly  greatly  facilitated    this    spread. 


90 


PNEUMONIAS  AND   [UTECTIONS  OF   RESPIRATOR*   TRACT 


Prom  the  data  available  it  is  impossible  to  stale  exactly 
when  and  by  which  patients  hemolytic  streptococcus  In- 
fection was  introduced  into  the  ward,  but  it  must  have  been 
very  early  since  the  death  rate  was  very  high  Prom  the  be- 
ginning, and  the  first  23  eases  coming  to  autopsy  died  with 
streptococcus  infection. 

Ward  1  was  opened  on  September  24.  Prom  thai  date 
until  ( Ictober  2  no  cubicles  were  in  use  and  few  precautions 
were  taken  against  transfer  of  infection.  On  October  2 
cubicles  were  installed  and  ordinary  precautions  to  prevent 
transfer  of  infection  were  instituted.  On  October  6  the 
ward  was  closed  to  further  admissions.  The  data  pre- 
sented in  Table  XX  are  divided  into  two  periods,  because 
on  September  29  and  30,  4  patients  with  streptococcus  pneu- 
monia were  admitted  to  the  ward. 


Table  XX 

Pneumonia  in  "Ward  1 


AVERAGE 

NIW!  BER  OF 
PATIENTS 
l\    WARD 

NUMBER    OP 

PATIENTS 

ADMITTED 

TOTAL 

DEATHS 

CULTURES   AT   AUTOPSY 

AMONG     PATIENTS 
ADMITTED     DURING 
THE     CORRESPOND- 
ING   PERIOD 

PNEUMO- 
COCCUS 

HI     ^ 

S  Q  <  s* 
S  y.  o  £ 

B    Z    y-   O 

NUMBER 

PER   CENT 

D 

Sept. 

24-29 
Sept.  30 

—Oct.  5 

35.8 
55.3 

34 

40 

11 
24 

32.3 

fiO.O 

5 

6 

3 

14 

3 

4 

During  tlie  first  period  from  September  24  to  29  the  ward 
contained  an  average  of  35.8  patients,  being  only  mod- 
erately crowded;  34  cases  of  pneumonia  were  admitted,  of 
whom  11  died,  a  mortality  of  32.3  per  cent.  It  is  note- 
worthy that  deaths  among  this  group  which  occurred  prior 
to  September  30  were  due  to  pneumococcus  infection  with 
one  exception,  a  patient  entering  the  ward  on  September  26 
and  dying  the  following  day.  Of  the  other  2  patients  in 
this  group  who  died  Avitli  hemolytic  streptococcus  pneu- 
monia, 1  was  admitted  to  the  ward  on  September  25,  was 


SECONDARY  INFECTION  IN  WARD  TREATMENT 


91 


shown  to  be  free  from  S.  hemolyticus  on  September  30,  and 
died  on  October  12  with  a  secondarily  acquired  streptococ- 
cus pneumonia  and  empyema;  the  other  was  admitted  on 
September  29  with  streptococcus  pneumonia  and  died  the 
following  day. 

During  the  second  period  from  September  30  to  October 
5  the  ward  contained  an  average  of  55.3  patients,  being 
very  overcrowded;  40  new  cases  of  pneumonia  were  ad- 
mitted of  whom  24  died,  a  mortality  of  60  per  cent.  Cul- 
tures taken  at  autopsy  showed  that  6  died  of  pneumococcus 
pneumonia,  14  with  hemolytic  streptococcus  infection.  As 
in  Ward  2,  patients  admitted  to  this  ward  were  in  no  way 
selected  and  were  probably,  as  experience  has  shown,  in 
large  part  pneumococcus  pneumonias  at  time  of  admission. 
The  widespread  dissemination  of  hemolytic  streptococcus 
and  its  fatal  effect  following  the  introduction  of  the  organ- 
ism on  September  29  and  30  is  only  too  evident. 

Secondary  Infection  with  Pneumococcus  in  Pneumonia 

The  foregoing  studies  have  shown  that  hemolytic  strep- 
tococcus infection  may  spread  by  contagion  throughout  an 
entire  ward  with  great  rapidity.  Other  observations  have 
demonstrated  that  pneumococcus  infection  may  be  trans- 
mitted in  the  same  way.  Only  three  instances  of  this  nature 
will  be  cited.  The  first  occurred  in  Ward  3  (Table  XXI). 
Between  September  6  and  16  no  cases  of  pneumonia  caused 


Table  XXI 

Secondary  Infection  with  Pneumococcus 
Type  II 


BED    OCCU- 
PIED 

ADMITTED 

PNEUMO- 
COCCUS  IN 
SPUTUM   ON 
ADMISSION 

SECONDARY 

INFECTION 

NAME 

DATE 

PNEUMO- 
COCCUS    AT 
AUTOPSY 

Pvt.  Wolfe 
Pvt.   Pullam 
Pvt.    Swain 

No.  6 
No.  5 
No.  3 

Sept.  17 
Sept.     9 
Sept.  16 

IV 

IV 

II 

Sept  23 
Sept.  24 

II* 
II 

'Isolated   by    blood   culture   on   Sept.    23.      Patient   recovered. 


92        PNEUMONIAS  AM'   [NFECTIONS  OF   RESPIRATORS  TRACT 

by  Pneumococcus  Type  II  had  been  admitted  to  the  ward. 
(>n  September  L6  Pvt.  Swain  was  admitted  to  the  ward  and 
placed  in  Bed  .">.  Bacteriologic  examination  of  his  sputum 
showed  that  his  pneumonia  was  caused  by  Pneumococcus 
Type  II.  At  this  time  Pvt.  Pullam,  who  had  been  ad- 
mitted to  the  ward  on  September  !•  with  a  pneumococcus 
Type  1 V  pneumonia,  occupied  Bed  5  separated  from  Bed  3 
by  one  intervening  bed.  lie  had  had  his  crisis  on  Septem- 
ber 14  and  was  doing  well,  his  temperature  being  normal. 
On  September  24  lie  developed  a  second  attack  of  pneu- 
monia and  died  on  September  30.  Cultures  at  autopsy 
showed  Pneumococcus  Type  II  in  heart's  blood  and  lung, 
Pneumococcus  Type  II  and  B.  influenzae  in  the  right  bron- 
chus. Pvt.  Wolfe  was  admitted  to  the  ward  with  broncho- 
pneumonia on  September  17  and  placed  in  Bed  6  next  to 
Pvt.  Pullam.  Pneumococcus  Type  IV  and  B.  influenza1 
were  found  in  his  sputum.  Mis  temperature  had  fallen  to 
normal  by  lysis  on  September  21  and  he  was  doing  well. 
On  September  23  his  temperature  suddenly  rose  and  he 
developed  a  second  attack  of  pneumonia.  Pneumococcus 
Type  II  was  isolated  by  blood  culture  on  this  date.  He 
recovered.  In  both  instances  Pneumococcus  Type  II  was 
acquired  after  the  admission  of  a  patient  with  a  Pneumo- 
coccus Type  II  pneumonia,  the  opportunity  for  contact  in- 
fection having  been  favored  by  the  association  of  these 
patients  in  adjoining  beds. 

The  second  instance  is  almost  identical  and  occurred  on 
the  opposite  side  of  Ward  3  at  about  the  same  time  (Table 
XXT1).  Pvt.  Linehan  was  admitted  on  September  16  and 
placed  in  Bed  30.  Pneumococcus  Type  IV  was  found  in 
his  sputum.  Pvt.  Thompson  was  admitted  the  following 
day  with  a  Pneumococcus  II  atypical  pneumonia  and  placed 
in  Bed  28.  The  next  day  Pvt.  Smith  was  admitted  and 
placed  in  Bed  26.  Pneumococcus  Type  IT  was  found  in 
his  sputum.  On  September  1!)  Pvt.  Thompson  recovered 
by  crisis  and  was  doing  well.     On  September  21  lie  had  a 


SECONDARY  INFECTION  IN  WAIlli  TUKATMKNT 


93 


Table  XXII 

Secondary  Infection  with  Pneumococcus 
Type  II 


PNEUMO- 

SECONDARY 

INFECTION 

BED    OCCU- 
PIED 

ADMITTED 

COCCUS 
IN    SPUTUM 

NAME 

PNEUMO- 

ON    ADMIS- 

DATE 

COCCUS 

SION 

AT     AUTOPSY 

Fvt.    Smith 

No.  26 

Sept.  18 

II 

II 

Pvt. 

Thompson 

No.  28 

Sept.  17 

Atyp.  II 

Sept.  21 

II 

Pvt. 

Linehan 

No.  30 

Sept.  16 

IV 

Sept.  26 

II 

chill,  his  temperature  rose  to  104.4°  F.  and  he  developed  a 
second  attack  of  pneumonia.  He  died  on  September  29; 
cultures  at  autopsy  showing  Pneumococcus  Type  II  in 
heart's  blood  and  left  pleural  cavity,  Pneumococcus  Type 
II  and  B.  influenza?  in  bronchus  and  lung.  Pvt.  Linehan 
had  begun  to  improve  on  September  24  and  his  temperature 
was  falling  by  lysis.  On  September  26  he  became  worse, 
developed  signs  of  pericarditis  and  died  on  September  30. 
Cultures  from  lungs  and  bronchus  at  autopsy  showed  Pneu- 
mococcus Type  II  and  B.  influenzae.  In  both  instances  the 
fatal  secondary  infection  with  Pneumococcus  Type  II  was 
undoubtedly  acquired  from  Pvt.  Smith  in  the  nearby  bed. 
The  third  instance  occurred  in  Ward  8  (Table  XXIII). 
Pvts.  Lewis  and  Scott  were  admitted  on  September  21  and 
were  placed  in  adjoining  beds,  50  and  51.  Lewis  showed 
Pneumococcus  Type  I  in  his  sputum,  Scott  Pneumococcus 
II  atypical.  The  following  day  Pvts.  Pighee,  Jones,  and 
Columbus  were  admitted  and  given  Beds  48,  49  and  53  re- 
spectively. All  showed  Pneumococcus  II  atypical  in  the 
sputum.  Pvt.  Lewis  with  Pneumococcus  Type  I  pneu- 
monia recovered  by  crisis  on  September  29.  His  tempera- 
ture remained  normal  until  October  2  when  it  suddenly 
rose  to  104.2°  F.  He  developed  a  second  attack  of  pneu- 
monia and  died  on  October  8.  Cultures  at  autopsy  from 
heart's  blood  and  lung  showed  Pneumococcus  II  atypical, 
from  the  bronchus  Pneumococcus  II  atypical  and  B.  influ- 


94 


PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATOR'S  TRACT 


Tab]  i    Will 

-      >\i>\::y  Infection  with  Pneumococcus 
ii   Atypical 


BED    0CC1 
PIED 

ADMITTED 

PNEUMO- 
COCCUS 

1\     SPUTUM 

SECONDARY      INFECTION 

NAME 

I'NKl' MO- 

i>\       AMIS- 

DATE 

COCCUS 

SION 

AT     Al  TOPS'? 

Pvt.  Pighee 
Pvt.  Jones 

No.  48 
No.  49 

Sept.  22 
Sept.  22 

Atvp.  II 

Atvp.  ir 

Pvt.    Lewis 

No.  50 

Sept.  21 

i 

Oct.  2 

Atvp.  II 

Pvt.  Scotl 

No.  5 1 

Sept.  _'l 

Atvp.  ir 

Pvt. 

•  olumbus 

No.  53 

Sept.  22 

Atvp.  11 

enzse.  It  is,  of  course,  impossible  to  say  from  which  one 
of  his  neighbors  Pvt.  Lewis  acquired  his  second  pneumo- 
coccus infection. 

It  is  noteworthy  thai  these  instances  of  secondary  con- 
tact infection  with  pneumococei  occurred  in  wards  where 
every  precaution  was  supposedly  taken  to  prevent  trans- 
fer of  infection  from  one  patient  to  another.  It  is  true 
however  that  the  wards  were  greatly  overcrowded  al  the 
time.  Many  other  instances  of  secondary  pneumococcus 
infection  in  cases  of  pneumonia  following'  influenza  were 
encountered  in  which  it  was  impossible  to  trace  the  source 
of  infection,  many  combinations  of  different  types  of  pneu- 
mococcus being  found.  There  were  two  instances  in  which 
Pneumococcus  Type  IV  was  found  in  the  sputum  by  inocu- 
lation of  white  mice  shortly  after  onset  of  pneumonia, 
whereas  secondary  infection  with  other  types  was  found 
at  autopsy,  one  with  Pneumococcus  Type  II,  one  with  Pneu- 
mococcus Type  III.  In  2  cases  by  inoculation  of  white  mice, 
two  types  of  pneumococcus  were  round  simultaneously  in 
the  sputum  coughed  from  the  lung,  in  one  Pneumococ- 
cus Types  III  and  I.Y,  in  the  other  Pneumococcus  Types 
I  and  IV.  There  were  5  cases  in  which  two  types  of  pneu- 
mococcus were  found  in  cultures  at  autopsy  as  shown  in 
Table  XXI Y.  Combined  pneumococcus  infections  of  this 
nature  are  almost    never  encountered   in  pneumonia  occur- 


SECONDARY  INFECTION  IN  WARD  TREATMENT  95 

Table  XXIV 
Mixed   Pneumococcus   Infections   in    P'nei  vtonia 


CULTURES    AT    AUTOPSY 

heart's  blood 

BRONCHUS 

LU:  •' 

Pvt.  Gal. 

Fn.   Type  III 
B.  influenzae 
Staphylococcus 

Pn.  Type  III 
Pn.  Type  IV 
B.  influenzas 

Pvt.  Sug. 

Pn.   Type   III 

Pn.   Type   III 
Pn.  Type  IV 
B.  influenzae 

Staphylococcus 

Pn.    Type   III 
Pn.  Type  IV 
B.   influenzae 

Pvt.    Hig. 

S.  hemolytieus 

Pn.  Type  1 1 
Pn.  Type  IV 
S.  hemolytieus 
Staph,  aureus 

Pvt.  Can. 

Pn.   Type  I 

— 

Fn.   Type  III 
S.   hemolytieus 

Pvt.   Fer. 

Sterile 

Pn.  Type  IV 
B.  influenzas 
Staphylococcus 

Pn.  Type  I 
Pn.  Type  IV 
B.  influenza? 

ring  under  normal  conditions  in  the  absence  of  epidemic  in- 
fluenza. 

The  foregoing  data  show  that  infection  with  one  type  of 
pneumococcus  may  readily  be  superimposed  upon  or  closely 
follow  infection  with  another  type.  Cases  have  been  cited 
in  which  it  was  clearly  demonstrated  that  this  was  due  to 
contact  infection.  It  is  furthermore  evident  that  pneumo- 
nia caused  by  one  type  of  pneumococcus  affords  no  relia- 
ble immunity  against  pneumonia  caused  by  another  type. 
The  same  conditions  that  favored  the  spread  of  hemolytic 
streptococcus  infection  also  favored  the  transfer  of  pneu- 
mococcus infection  from  patient  to  patient. 

Secondary  Contact  Infection  in  Influenza 

The  material  so  far  presented  has  dealt  with  contact  in- 
fection in  cases  of  pneumonia  following  influenza.  That  a 
similar  contact  infection  in  cases  of  influenza  treated  in 
crowded  hospital  wards  is  responsible  in  considerable  de- 
gree for  the  development  of  pneumonia  in  cases  of  influ- 
enza seems  quite  probable.  It  has  already  been  stated  that 
this  pneumonia  was  found  in  large  part  to  be  caused  by 


96        PNEUMONIAS  AND   [NFECTIONS  01   RESPIRATOR'S  TRACT 

infection  with  types  of  pneumococcus  thai  are  found  in  the 

mouths  of  Dorma]  individuals.  Ii  1ms  been  fairly  definitely 
established  by  Stillman3  that  Lobar  pneumonia  caused  by 
pneumococcus  Types  1  and  II   is  in  all  probability  due  to 

contad  infection,  and  definite  instances  of  such  infection 
by  Pneumococcus  Type  11  have  been  reported  above.  In 
a  recent  communication  Stillman4  has  furthermore  shown 

thai  of  the  various  groups  of  Pneumococcus  II  atypical 
those  most  frequently  associated  with  pneumonia  are 
rarely  found  in  normal  mouths,  while  those  infrequently 
associated  with  pneumonia  are  more  commonly  found. 
Whether  similar  considerations  will  hold  true  for  pneu- 
mococci  of  Group  IV  can  only  be  determined  by  further 
investigation.  It  has  been  stated  that  certain  observations 
made  during  the  course  of  this  work  have  suggested  that 
cases  of  pneumonia  which  complicate  influenza  may  be  due 
to  contact  rather  than  to  autogenous  infection.  The  data 
available  are  far  too  limited  to  establish  this  fact  and  it 
would  require  a  very  extensive  study  to  furnish  conclusive 
evidence. 

Certain  general  observations  have  suggested  this  point 
of  view.  It  is  well  recognized  that  the  incidence  of  pneu- 
monia in  patients  with  influenza  has  been  much  higher 
where  overcrowding-  has  existed.  It  would  seem  probable 
that  this  has  been  in  large  part  due  to  the  greater  oppor- 
tunity for  the  dissemination  of  organisms  capable  of  pro- 
ducing pneumonia  and  the  consequently  increased  oppor- 
tunity for  secondary  contact  infection  among  patients 
treated  under  such  conditions.  The  not  infrequent  occur- 
rence of  influenzal  pneumonia  due  to  combined  infections 
of  the  different  types  of  pneumococci,  hemolytic  strepto- 
cocci, staphylococci,  and  other  bacteria,  instances  of  which 
have  been  cited,  is  in  harmony  with  this  view,  especially 
since  pneumonia  under  ordinary  conditions  is  rarely  found 
to  be  associated  with  mixed  infections  of  this  nature.     It 


'Stillman:     Tour.    Exper.   Med.,    1916.   xxiv,   651. 
4Stillman:     Jour.   Exper.    Med.,    1919,   xxix,  251. 


SECONDARY  INFECTION  IN   WAI!I>  TEEATMENT  97 

is  true  that  healthy  individuals  occasionally  carry  more 
than  one  type  of  pneumococcus  simultaneously  in  the 
mouth,  though,  this  is  very  infrequent,  and  autogenous  in- 
fection occurring  in  such  individuals  might  account  in 
some  instances  for  the  mixed  pneumococcus  infections  en- 
countered. By  way  of  analogy  it  lias  been  clearly  shown 
in  other  studies  by  the  Commission  on  the  relation  of  hem- 
olytic streptococcus  carriers  to  the  complications  of  mea- 
sles, that  secondary  infection  of  the  respiratory  tract  with 
S.  hemolyticus  is  in  very  large  part  due  to  contact  infec- 
tion, the  chronic  carrier  rarely  developing  complications 
due  to  this  organism. 

To  obtain  further  light  on  this  question  the  type  of  pneu- 
mococcus present  in  the  mouths  of  46  consecutive  cases  of 
early  uncomplicated  influenza  was  determined  by  the  mouse 
inoculation  method  at  time  of  admission  to  the  receiving 
ward  of  the  hospital  before  the  patients  had  been  associ- 
ated, with  the  purpose  of  determining  if  cases  among  this 
group  which  subsequently  developed  pneumonia  might  be 
shown  to  have  acquired  a  pneumococcus  which  they  did  not 
carry  at  time  of  admission.  This  group  of  patients  was 
treated  in  a  special  ward  set  apart  for  the  purpose.  The 
patients  were  assigned  to  beds  in  rotation  and  confined  in 
bed  until  thoroughly  convalescent.  Beds  were  well  separ- 
ated and  cubicles,  masks  and  gowns  were  in  use.  Cultures 
were  made  from  the  ward  personnel.  By  these  procedures 
an  accurate  record  was  kept  of  all  sources  of  pneumococcus 
infection.  The  types  of  pneumococcus  found  in  the  mouths 
of  these  patients  at  time  of  admission  are  shown  in  Table 
XXV. 

Only  1  patient  in  this  group  developed  pneumonia.  At 
time  of  admission  he  had  no  pneumococcus  in  his  mouth  as 
determined  by  inoculation  of  a  white  mouse  with  his  spu- 
tum. Examination  of  the  sputum  by  the  same  method  at 
time  of  onset  of  pneumonia  three  days  after  admission 
showed  Pneumococcus  Tj^pe  III.     The  only  ascertainable 


98 


PNEUMONIAS  AND   INFECTIONS  OF   RESPIRATORS  TRACT 

Table  XXV 
Types  op  Pneumococci  in  the  Mouths  of   Inpluenza  Patients 


i'\  ii   Mot  on  i  s 


xi  MBER 


PER  CENT 


PneumocoecuS;  Type  I 

(l 

0 

Pneumoeoccus,  Tj  pe   1 1 

0 

0 

Pneumococcus,   II   atypical 

1 

.)   o 

Pneumoeoccus,  Type  1 1 1 

0 

0 

Pneumococcus,  Group  I  V 

25 

54.3 

Xo   pneunioeoeci    found 

20 

43.5 

source  of  infection  in  this  case  was  our  of  the  ward  attend- 
ants who  carried  Pneumococcus  Type  III  in  his  throat  in 
sufficiently  large  numbers  to  be  demonstrable  by  direct  cul- 
ture and  who  frequently  came  in  contact  with  the  patient. 
In  tins  instance  the  development  of  pneumonia  was  prob- 
ably due  to  contact  infection.  An  extensive  study  of  this 
nature  would  be  necessary  to  determine  in  what  proportion 
of  cases  pneumonia  following  influenza  is  caused  by  second- 
ary contact  infection  and  in  what  proportion  to  autogenous 
infection.  It  is  at  least  evident  that  contact  infection  with  a 
type  of  pneumococcus  found  in  the  mouth  of  normal  indi- 
viduals may  occur  in  influenza  and  be  responsible  for  the 
development  of  pneumonia.  Therefore  every  precaution 
should  be  taken  to  prevent  it. 

Methods  for  the  Prevention  of  Secondary  Contact  Infection 
in  Influenza  and  Pneumonia 

The  methods  at  present  in  vogue  for  preventing  the 
spread  of  contagion  in  wards  devoted  to  the  care  of  patients 
with  influenza  and  pneumonia  may  be  briefly  enumerated: 
The  separation  of  patients  by  means  of  sheet  or  screen 
cubicles,  the  wearing  of  masks  and  gowns  by  the  ward  per- 
sonnel and  to  some  extent  by  convalescent  patients  who  are 
up  and  about  the  ward,  and  in  some  hospitals  the  separa- 
tion of  streptococcus  carriers  from  noncarriers  as  deter- 
mined by  throat  culture  at  time  of  admission.  That  these 
methods  are  of  some  value  in  preventing  spread  of  infec- 
tion cannot  be  denied,  and  it  is  probable  that  they  are  fairly 


SECONDARY  INFECTION   IN  WARD  TREATMENT  99 

effective  under  ordinary  conditions  when  conscientiously 
carried  out.  That  they  inevitably  break  down  in  the  pres- 
ence of  an  overwhelming  epidemic  when  hospital  wards 
become  overcrowded  is  only  too  evident.  Under  such  con- 
ditions the  sheets  hung  between  the  beds  are  constantly  be- 
ing displaced  and  are  slight  proof  against  a  patient's  curi- 
osity as  to  the  identity  and  condition  of  the  man  in  the;  ad- 
joining bed;  masks  cannot  be  worn  by  patients  seriously 
ill  with  pneumonia,  during  the  very  time  when  they  are 
most  dangerous  and  in  greatest  danger  and  those  worn  by 
the  ward  personnel  are  very  rarely  sufficiently  well  made 
to  prevent  spread  of  contagion  by  droplet  infection  as  the 
studies  of  Haller  and  Colwell5  and  Doust  and  Lyon6  have 
shown;  the  separation  of  streptococcus  carriers  from  non- 
carriers  as  at  present  carried  out  cannot  keep  pace  with  the 
ever  increasing  influx  of  patients  nor  with  the  rapidity  of 
the  spread  of  the  hemolytic  streptococcus,  in  part  because 
of  the  time  required  to  make  the  bacteriologic  diagnosis,  in 
part  because  the  amount  of  work  involved  cannot  be  accom- 
plished by  the  laboratory  personnel  available.  That  this  is 
so  will  be  shown  in  data  presented  below.  Not  only  do 
these  methods  break  down  in  the  face  of  an  epidemic,  but 
they  often  provide  a  false  sense  of  security. 

In  searching  for  a  solution  of  the  problem  it  is  essential 
to  have  the  following  considerations  clearly  in  mind.  Ev- 
ery patient  with  influenza  must  be  considered  a  potential 
source  of  pneumococcus  or  hemolytic  streptococcus  infec- 
tion for  his  neighbor  until  he  is  proved  otherwise  by  bac- 
teriologic examination.  Every  person  engaged  in  the  care 
of  patients  with  respiratoiy  diseases  must  also  be  regarded 
as  a  potential  source  of  danger.  Pneumonia  cannot  be  re- 
garded as  one  disease  but  must  be  looked  upon  as  a  group 
of  different  diseases,  with  more  or  less  similar  physical 
signs  and  symptoms,  it  is  true,  but  caused  by  a  considerable 
variety  of  bacteria,  infection  with  any  one  of  which  not 

EHaller   and    Colwell:     Jour.    Am.    Med.    Assn.,    1918,    lxxi,    1213. 
"Doust  and  Lyon:     Jour.    Am.   Med.  Assn.,    1918,   lxxi,    1216. 


100      PNEUMONIAS  AND    [NFECTIONS  OF   RESPIRATORS  TRACT 

only  provides  qo  protection  againsi  infection  with  another, 

inn  may  even  render  the  individual  more  susceptible  to 
secondary  infection.  Therefore,  every  patienl  with  pneu- 
monia musl  be  regarded  as  an  actual  source  of  danger  to 
his  neighbor,  at  least  until  it  is  established  that  he  has  the 
same  type  of  infection.  All  these  considerations  are  espe- 
cially true  iii  the  presence  of  influenza,  for  it  has  become 
evident  thai  many  organisms  readily  gain  access  to  the 
lung  and  produce  pneumonia  in  patients  with  influenza 
which  under  ordinary  circumstances  fail  to  cause  disease 
of  t he  respiratory  organs. 

Since  secondary  infection  in  respiratory  disease  is  un- 
doubtedly spread  in  large  part  by  droplet  and  contact  in- 
fection, the  prevention  of  secondary  infection  must  depend 
upon  the  elimination  of  these  methods  of  transmission. 
Three  solutions  present  themselves:  (1)  Ward  treatment 
with  absolute  elimination  of  overcrowding  and  much  wider 
separation  of  patients  than  has  hitherto  been  deemed  nec- 
essary; (2)  segregation  of  patients  according  to  type  of 
bacterial  infection;  (3)  effective  individual  isolation  of 
every  patient. 

It  has  been  clearly  shown  that  treatment  of  influenza  and 
pneumonia  in  overcrowded  wards  even  with  the  use  of  such 
precautions  to  prevent  transfer  of  infection  as  cubicles, 
masking  of  attendants  and  patients,  etc.,  is  attended  by  se- 
rious danger  of  contact  infection  and  that  such  infection 
will  almost  inevitably  occur.  This  is  not  at  all  surprising 
when  it  is  remembered  that  we  are  treating  in  the  same 
ward,  in  the  case  of  pneumonia,  a  group  of  what  are  in  real- 
ity entirely  different  diseases,  all  of  which  may  be  trans- 
mitted from  one  patient  to  another,  and  in  the  case  of  in- 
fluenza a  group  of  individuals  who  carry  a  variety  of 
potentially  pathogenic  bacteria.  No  one  would  expect  to 
treal  cases  of  scarlet  fever,  measles,  and  diphtheria  to- 
gether in  a  hospital  ward  without  having  contact  infection 
result.     Among  patients  ill   with    influenza   and   postinflu- 


SECONDARY   INFECTION    IN    WAED  TREATMENT  101 

enzal  pneumonia,  certainly  streptococcus  pneumonia  and 
to  some  extent  pneumococcus  pneumonia  may  be  transmil 
ted  quite  as  readily  as  any  of  these  diseases.  In  view  of 
these  considerations  it  must  be  apparent  if  ward  treatment 
of  these  diseases  is  to  be  continued  without  respect  to  type 
of  bacterial  infection,  not  only  that  overcrowding  is  abso- 
lutely contraindicated  but  also  that  much  wider  separation 
of  patients  than  has  hitherto  been  regarded  as  necessary 
is  imperative.  Furthermore,  beds  should  be  separated  by 
permanent  cubicles  that  cannot  readily  be  displaced.  Pa- 
tients should  be  confined  to  their  cubicles  until  thoroughly 
convalescent  and  when  up  and  about  should  not  be  allowed 
to  enter  cubicles  occupied  by  patients  still  sick.  Medical 
officers,  nurses  and  attendants  who  come  into  contact  with 
the  patients  should  use  the  same  rigid  precautions  that  are 
used  in  the  care  of  patients  with  typhoid  or  erysipelas  or 
meningitis  with  the  additional  use  of  means  to  prevent 
droplet  infection  of  the  patients,  always  bearing  in  mind 
that  the  respiratory  tract  in  patients  with  influenza  or 
postinfluenzal  pneumonia  is  as  susceptible  to  secondary 
infection  as  the  postpartum  uterus  or  an  open  surgical 
wound.  In  other  words,  the  most  rigid  aseptic  technic 
should  be  maintained.  The  recognition  of  a  case  of  strep- 
tococcus pneumonia  in  a  ward  should  be  an  indication  for 
immediate  quarantine  of  the  ward  until  it  has  been  shown 
by  bacteriologic  examination  that  there  is  no  longer  danger 
of  spread  of  streptococcus  contagion.  This  is  done  in  the 
case  of  meningitis  or  diphtheria,  neither  of  which  diseases 
is  comparable  with  streptococcus  pneumonia  in  rapidity 
of  spread  or  in  resulting  fatality. 

Segregation  of  patients  in  wards  according  to  type  of 
bacterial  infection  while  theoretically  an  improvement  over 
the  indiscriminate  mixing  of  patients  with  many  different 
types  of  infection  presents  many  practical  difficulties  which 
make  it  impossible  to  carry  out  in  the  presence  of  an  over- 
whelming epidemic.     It  is  quite  obvious  that  grouping  of 


L02      PNEUMONIAS  AN'h   INFECTIONS  OF  RESPIRATOR'S  TRACT 

influenzal  patients  on  the  basis  of  the  types  of  pneumococci 
thai  they  carry  in  their  mouths  is  impossible  since  the  greal 
majority  of  mouth  pneumococci  belong  to  Group  IV  and 
comprise  a  heterologous  immunologic  group.  The  separa- 
tion of  influenza  patients  who  carry  S.  hemolyticus  Iron) 
those  who  do  nol  would  appear  to  offer  a  more  hopeful  field. 
since  we  cannot  make  an  immediate  distinction  between 
streptococcus  carriers  and  aoncarriers  by  inspection  of  the 
patient,  this  procedure  requires  the  taking  of  throat  cul- 
tures at  time  of  admission  to  the  hospital,  the  holding  of 
patients  for  eighteen  to  twenty-four  hours  in  receiving 
wards  until  the  bacteriologic  diagnosis  lias  been  made,  and 
their  subsequent  distribution  to  streptococcus  and  non- 
streptococcus  wards.  This  is  feasible  when  the  admission 
rate  is  low  and  the  aumber  of  streptococcus  carriers  found 
at  time  of  admission  is  small.  In  the  presence  of  an  influ- 
enza epidemic  it  immediately  becomes  impossible  to  carry 
out  in  base  hospitals  as  now  constituted,  since  the  demand 
for  beds  under  such  conditions  at  once  converts  a  large 
part  of  the  hospital  into  a  group  of  receiving  wards  with 
little  room  remaining  for  subsequent  separation  of  patients. 
The  amount  of  bacteriologic  work  involved  at  once  be- 
comes prohibitive  and  the  time  required  to  make  the  bac- 
teriologic diagnosis  defeats  its  purpose  since  it  allows  the 
spread  of  hemolytic  streptococcus  to  occur  in  the  receiving- 
wards  during  the  interval. 

The  foregoing  statements  are  based  on  results  obtained 
in  an  attempt  to  separate  streptococcus  carriers  from  non- 
carriers  in  a  limited  group  of  cases  of  influenza  at  Camp 
Pike,  the  investigation  being  conducted  during  a  secondary 
wave  of  influenza  between  November  27  and  December  5.  A 
special  group  of  five  wards  consisting  of  one  receiving 
ward  and  four  distributing  wards  were  set  aside  for  the 
study.  Cubicles,  masks  and  gowns  were  in  use  and  the 
wards  were  not  crowded.  The  personnel  on  these  wards  did 
not  carry  S.  hemolyticus  in  their  throats.   Patients  entering 


SECONDARY    INFECTION    IN    VVAIMJ   TKKATMENT 


1  0?> 


the  receiving  ward  were  assigned  to  beds  in  rotation. 
Throat  cultures  were  made  on  blood  agar  plates  at  time  of 
admission.  The  plates  were  examined  promptly  the  next 
morning,  the  diagnosis  of  S.  hemolyticus  being  made  by  the 
characteristic  hemolytic  colonies  and  microscopic  examina- 
tion of  stained  smears.  By  this  method  a  report  reached 
the  receiving  ward  at  9 :30  a.m.  and  patients  were  promptly 
evacuated  to  the  streptococcus  and  nonstreptococcus  wards, 
where  they  were  again  assigned  to  beds  in  rotation,  re- 
maining confined  in  bed  until  convalescent.  Confirmation 
of  all  strains  of  hemolytic  streptococcus  was  subsequently 
carried  out  by  isolation  in  pure  culture,  bile  solubility  test, 
and  hemolytic  test  with  washed  sheep  corpuscles.  All  cases 
free  from  hemolytic  streptococci  at  time  of  admission  who 
were  sent  to  the  " clean"  wards  were  recultured  daily 
throughout  the  period  of  study,  those  acquiring  a  hemo- 
lytic streptococcus  being  transferred  to  a  streptococcus 
ward  as  soon  as  the  bacteriologic  diagnosis  was  made. 
The  results  are  shown  in  Table  XXVI. 

Table  XXVI 
S.  Hemolyticus  in  Cases  of  Influenza 


DATE 

PATIENTS 
ADMITTED 
TO  RECEIV- 
ING   WARD 

THROAT 
CULTURES 
ON   ADMIS- 
SION.       S. 

'  '  CLEAN  '  'CASES     ACQUIR- 
ING    S.     HEMOLYTICUS     IN 
THE   HOSPITAL 

HEMOLY- 
TICUS : 

WHILE     IN 
REC.     "WARD 

"WHILE     IN 

"CLEAN" 

WARD 

TOTAL 

+ 

- 

Nov.  27 

12 

4 

8 

0 

2 

2 

Nov.  28 

8 

2 

6 

0 

1 

1 

Nov.  29 

17s 

8 

9 

1 

2 

3 

Nov.  30 

11 

9 

9 

3 

0 

3 

Dec.    1 

10 

5 

5 

0                       0 

0 

Dec.    2 

37 

16 

21 

1                       1 

2 

Dec.    3 

21 

8 

13 

0                       2 

2 

Dec.    4 

32* 

11 

21 

4                       2 

6 

Dec.    5 

17 

10 

7 

5                       0 

5 

Totals 

165 

66 

99 

14                     10 

24 

*Held   in    receiving   ward    40    hours    because    of   admission    of    case   of    meningococcus 
meningitis   to  ward  by  mistake. 

One  hundred  and  sixty-five  cases  were  admitted  to  the 
receiving  ward  during  the  period  of  study  as  cases  of  influ- 


L04      PNEUMONIAS   AND    ENFECTIONS  OF   RESPIRATORS   TRACT 

enza.  Of  these,  L37  had  infhienza;  4  of  those  with  influenza 
had  pneumonia  at  time  of  admission,  23  had  acute  follicular 
tonsillitis,  •!  epidemic  cerebrospinal  meningitis,  1  scarlel 
fever,  and  1  Vincent's  angina.  Sixty-six  cases  (-10  per  cent) 
showed  hemolytic  streptococcus  in  the  throai  at  time  of 
admission  and  were  sent  to  the  streptococcals  wards;  99 
cases  (60  per  cent)  were  negative  for  hemolytic  streptococ- 
cus on  admission,  and  of  these  91  were  sent  to  the  "clean"' 
influenza  wards.  Twenty-four  of  these  clean  cases  subse- 
quently became  positive  for  S.  hemolyticus.  It  is  especially 
noteworthy  that  14  of  them  acquired  a  hemolytic  strepto- 
coccals during  the  short  period  that  they  were  held  in  the 
receiving  ward  awaiting  the  report  of  the  culture  taken  at 
time  of  admission,  the  first  culture  taken  shortly  after  ad- 
mission to  tin1  "clean"  wards  being  positive.  This  result 
was  undoubtedly  due  to  the  fact  that  these  cases  were  un- 
avoidably associated  in  the  receiving  ward  with  many  car- 
riers of  hemolytic  streptococcus.  It  is  evident  that  cases 
which  were  supposedly  free  from  streptococci  but  which  in 
reality  had  picked  up  the  organism  in  the  receiving  ward 
were  constantly  being  sent  to  the  "clean"  wards.  It  is 
furthermore  evident  that  if  the  precaution  had  not  been 
taken  of  reculturing  all  clean  cases  on  day  of  admission 
to  the  "clean"  wards  and  daily  thereafter  these  wards 
would  soon  have  become  saturated  with  hemolytic  strep- 
tococci. Even  under  these  conditions,  10  cases,  after  vary- 
ing periods  in  the  "clean"  wards,  acquired  the  organism  in 
their  throats.  When  it  is  stated  that  it  required  the  full 
time  of  two  men  under  very  special  conditions  to  carry  out 
this  work  in  a  very  limited  number  of  cases  and  that  it 
failed  to  keep  "clean"  wards  free  from  hemolytic  strepto- 
cocci, it  is  only  too  apparent  that  the  efficient  separation  of 
carriers  from  noncarriers  in  the  presence  of  an  epidemic  of 
influenza  is  an  impossible  task. 

The  segregation  of  pneumococcus  pneumonias  following 
influenza  according  to  type  of  infection  is  obviously  impos- 


SECONDARY  INFECTION    IN    WARD  TREATMENT  L05 

sible,  since  they  are  caused  by  an  almost  unlimited  variety 
of  immunologic  types  as  far  as  presenl  knowledge  goes. 

Even  the  efficient  separation  of  streptococcus  pneumo- 
nias from  pneumococcus  pneumonias  would  require  a  con- 
siderable team  of  workers  and  the  closest  cooperation  be- 
tween laboratory  and  ward  staffs,  so  that  no  case  of  pneu- 
monia would  be  sent  to  a  pneumonia  ward  until  the  bacte- 
riologic  diagnosis  had  been  made.  In  our  experience  this  is 
rarely  considered  feasible  even  under  ordinary  conditions, 
and  in  the  presence  of  an  epidemic  is  nearly  impossible  be- 
cause of  the  volume  of  work  involved  and  the  delay  neces- 
sitated by  bacteriologic  methods.  It  is,  nevertheless,  abso- 
lutely essential  if  highly  fatal  ward  epidemics  of  strepto- 
coccus pneumonia  are  to  be  prevented. 

In  view  of  the  considerations  discussed  above,  it  is  be- 
lieved that  the  clear  and  most  fundamental  indication  for 
the  management  of  epidemic  respiratory  diseases  in  the 
army  is  to  scatter  patients  as  widely  as  possible  instead  of 
following  the  time-honored  custom  of  concentrating  them. 
In  brief,  abandon  open  ward  treatment  and  adopt  effective 
individual  isolation  of  every  case,  maintaining  as  strict  a 
quarantine  as  is  demanded  in  other  highly  contagious  and 
infectious  diseases.  The  adoption  of  a  strict  aseptic  tech- 
nic  in  the  handling  of  these  patients  is  an  evident  corollary. 
Only  by  this  means  can  the  serious  and  highly  fatal  second- 
ary hospital  infections,  which  occur  in  influenza  and  pneu- 
monia when  these  diseases  are  present  in  epidemic  form, 
be  prevented. 

The  prevention  of  secondary  infection,  prior  to  admis- 
sion to  the  hospital,  is  another  and  more  difficult  problem. 
That  opportunity  for  secondary  contact  infection  in  cases 
of  influenza  before  patients  reach  the  hospital  is  great 
seems  unquestionable,  since  many  cases  have  already  de- 
veloped these  infections  at  time  of  admission.  During  the 
epidemic  patients  were  crowded  in  regimental  infirmaries, 
in  ambulances,  and  in  the  receiving  office  of  the  hospital 


106      PNEUMONIAS   ANh    INFECTIONS  OF   RESPIRATOR'S   TRACT 

with  every  opportunity  for  droplel  infection  present.     No 

study  has  been  made  of  this  question,  hut  it  seems  reason- 
able that  the  same  methods  of  prevention  should  apply, 
namely,  effective  separation  of  patients. 

It  is  not  within  the  scope  of  this  paper  to  discuss  details 
of  method,  hut  anything  that  is  possible  becomes  feasible 
as  soon  as  suflicient  evidence  can  be  broughl  to  hear  thai 
it  is  a  necessity.  In  the  present  instance  it  would  seem  that 
any  means  that  can  be  used  to  reduce  materially  the  ter- 
rific toll  taken  by  respiratory  diseases  is  an  absolute  neces- 
sity. 

Summary 

1.  Secondary  contact  infection  with  pneumococci  not  in- 
frequently occurs  in  patients  with  pneumonia  following  in- 
fluenza when  they  are  treated  in  hospital  wards. 

2.  Secondary  contact  infection  with  S.  hemolyticus  read- 
ily occurs  in  patients  with  pneumonia  and  may  spread 
rapidly  throughout  an  entire  ward  with  highly  fatal  results. 

3.  Secondary  contact  infection  may  be  responsible  for 
the  development  of  pneumonia  in  patients  with  influenza. 

4.  Ward  treatment  of  these  diseases  is  fraught  with  se- 
rious danger  which  is  greatly  increased  by  overcrowding, 
by  imperfect  separation  of  patients  by  cubicles,  and  by 
imperfect  aseptic  technic  of  medical  officers,  nurses,  and 
attendants. 

5.  It  is  probable  that  secondary  contact  infection  can  be 
effectively  prevented  only  by  individual  isolation  and  strict 
quarantine  of  every  patient. 


CHAPTER  IV 

THE  PATHOLOGY  AND  BACTERIOLOGY  OF  PNEU- 
MONIA FOLLOWING  INFLUENZA 

E.  L.  Opie,  M.D. ;  F.  G.  Blake,  M.D. ;  and  T.M.  Rivers,  M.D. 

Many  observers  have  described  isolated  phases  of  the 
recent  epidemic  and  of  past  epidemics  of  influenza.  Few 
have  had  an  opportunity  to  follow  the  pathology  of  influ- 
enza from  the  onset  of  an  epidemic  through  a  period  of  sev- 
eral months  and  to  observe  the  succession  of  acute  and 
chronic  changes  which  occur  in  the  lungs.  Our  commission 
arrived  on  September  5, 1918,  at  Camp  Pike  two  weeks  be- 
fore the  outbreak  of  influenza.  The  commission  had  pre- 
viously made  a  careful  study  of  the  clinical  course,  the  bac- 
teriology and  to  a  limited  extent  the  pathology  of  pneu- 
monia occurring  at  Camp  Funston  where  there  was  little 
if  any  influenza.  Study  of  the  records  preserved  at  the 
base  hospital  at  Camp  Funston  had  convinced  us  that  this 
camp  had  passed  through  an  epidemic  of  influenza  dur- 
ing the  spring  of  1918,  this  epidemic  being  followed  by 
a  very  severe  outbreak  of  pneumonia.  Our  investigation 
at  Camp  Funston  had  brought  to  our  attention  those 
phases  of  pneumonia  which  with  the  facilities  of  a  base 
hospital  laboratory  could  be  most  profitably  studied  with  a 
view  to  determining  the  causation,  the  epidemiology  and 
the  prevention  of  the  pneumonias  prevalent  in  the  Amer- 
ican army. 

Study  of  pneumonia  after  death  offers  the  only  oppor- 
tunity of  determining  the  relation  of  pulmonary  lesions 
to  the  considerable  variety  of  microorganism  associated 
with  them.  Clinical  diagnosis  furnishes  no  certain  crite- 
rion for  distinguishing  lobar  and  bronchopneumonia:  sup- 

107 


L08      PNEUMONIAS  ANIt   [NFECTIONS  OF   RESPIRATORS   TRACT 

purative  pneumonia  is  rarely  recognizable  during  life. 
The  relation  of  pneumococci,  streptococci,  staphylococci  or 
I),  influenzas  1<>  one  or  other  t\  pe  of  pneumonia  can  be  deter- 
mined with  accuracy  only  after  death;  for  the  demonstra- 
tion of  one  or  more  of  these  micro  organisms  in  material 
obtained  Prom  the  upper  respiratory  passages  in  life, 
though  of  value,  furnishes  us  no  definite  evidence  thai  the 
organism  which  lias  been  identified  lias  entered  the  lung 
and  passed  from  the  bronchi  to  produce  pneumonia. 

Study  of  autopsies  following  examination  of  the  sputum 
during  life  has  shown  that  an  individual  primarily  attacked 
by  influenza  may  suffer  with  a  succession  of  pneumonias, 
one  microorganism  having  prepared  the  way  Tor  another. 
The  complexity  of  the  subject  is  much  increased  by  the 
truth  that  pyogenic  microorganisms,  like  the  tubercle 
bacilli,  are  capable  of  producing  a  considerable  variety  of 
pulmonary  lesions. 

Examination  of  the  lungs  of  a  large  number  of  individuals 
who  have  died  as  the  result  of  pneumonia  following  in- 
fluenza lias  disclosed  a  succession  of  acute  and  chronic  dis- 
eases. Immediately  succeeding  the  height  of  the  epidemic 
of  influenza,  death  occurred  with  acute  lobar  pneumonia 
or  with  diffusely  distributed  hemorrhagic  bronchopneumo- 
nia caused  in  the  majority  of  instances  by  Pneumococcus 
IV  in  association  with  B.  influenzae.  Superimposed  infec- 
tion with  hemolytic  streptococci  increased  in  frequency  and 
in  individuals  who  had  occupied  certain  wards  was  almost 
invariable.  At  a  later  period,  from  one  to  two  months  fol- 
lowing the  maximum  incidence  of  influenza  chronic  lesions, 
namely,  bronchiectasis,  unresolved  pneumonia,  and  chronic 
empyema  were  common  and  often  occurred  as  the  result 
of  influenza  which  had  had  its  onset  at  1  lie  height  of  the  epi- 
demic. 

When  influenza  attacked  the  encampment,  about  50,000 
troops  were  quartered  in  it,  and  for  a  considerable  period 
no  more  troops  were  brought  into  the  camp  and  none  left 


PATHOLOGY  AND  BACTERIOLOGY    FOLLOWING    I  N  KM  '  K.N'XA      L09 

it.  All  cases  of  pneumonia  occurring  anions  those  i  coops 
were  brought  to  the  base  hospital  so  that  the  autopsies 
which  were  studied  were;  ropresonljitivo  of  ;ill  the  pneu- 
monias following  influenza  in  this  limited  group  of  men. 
It  is  noteworthy  that  autopsy  disclosed  no  instance  of  fatal 
influenza  unaccompanied  by  pneumonia. 

Pneumonia  of  Influenza, — Knowledge  concerning  the  bac- 
teriology of  the  pneumonia  of  influenza  dates  from  the 
study  of  the  epidemic  of  1889-90.  The  frequency  with 
which  Diplococcus  lanceolatus  occurred  in  association  with 
influenzal  pneumonia  was  well  recognized,  although  several 
observers,  notably  Finkler1  and  Ribbert,2  found  Streptococ- 
cus pyogenes  so  often  that  they  attributed  the  pneumonia 
of  influenza  to  this  microorganism. 

During  a  subsidiary  outbreak  of  influenza  occurring  in 
1891-92  Pfeiffer3  discovered  the  microorganism  which  he 
believed  was  the  cause  of  the  disease.  Pneumonia,  he  be- 
lieved, was  caused  by  the  invasion  of  this  microorganism 
into  the  lung,  and  the  pneumonia  of  influenza,  if  death  oc- 
curred at  the  height  of  the  disease,  was  characterized  not 
only  by  the  presence  of  the  bacillus  of  influenza,  but  was 
recognizable  by  its  anatomic  peculiarities.  He  described 
lobular  patches  of  consolidation  which  were  separated  from 
one  another  by  air  containing  tissue  or  were  confluent,  so 
that,  although  the  lobular  character  was  still  recognizable, 
whole  lobes  might  be  affected.  The  consolidated  tissue 
was  dark  red  and  within  each  lobular  area  were  small,  yel- 
lowish gray  spots  varying  in  size  from  that  of  a  pinhead  to 
a  pea.  In  the  mucus  of  the  larynx  and  trachea  were  nu- 
merous microorganisms,  including  diplococci  and  strepto- 
cocci, among  which  influenza  bacilli  were  predominant ;  in 
the  larger  bronchi,  bacteria  other  than  influenza  bacilli 
were  less  abundant,  whereas  in  the  finer  bronchi  filled  with 


1Finkler,   D.:     Infectionen  der  Lunge   durch   Streptococcen  und   Influenza   Bacillen,   Bonn, 

1895. 
2Ribbert:     Anatomische     und     bacteriologische     Beobachtungen     iiber     Influenza.     Deutsch. 

med.    Wchnschr.,    1890,   xvi.   61,   301. 
3Pfeiffer:     Die   Aetiologie   der   Influenza,   Ztschr.   f.    Hyg.    1893,   xiii,    357. 


110      PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATOR'S  TRACT 

purulent  fluid  and  in  the  lung  tissue  influenza  bacilli  had 
undivided  sway.  Pfeiffer  slated  that  the  changes  de- 
scribed were  found  when  death  occurred  at  the  height  of 
the  disease,  whereas  other  pulmonary  lesions  might  be 
sequelae  of  this  typical  influenzal  pneumonia. 

Observations  upon  the  pathology  of  influenzal  pneumonia 
made  during  the  epidemic  of  1889-92  have  been  collected 
in  the  monograph  of  Leichtenstern4  published  in  1896.  He 
combats  the  opinion  held  by  some  observers  that  pneumonia 
with  influenza  is  always  catarrhal  and  cites  many  writers 
to  prove  that  lobar  pneumonia  not  infrequently  accom- 
panies the  disease.  Indeed,  some  have  found  "croupous" 
pneumonia  more  often  than  "catarrhal."  Krannhals8 
at  Riga  found  typical  fibrinous  pneumonia  in  53  instances, 
doubtful  forms  in  22  and  bronchopneumonia  in  37.  Cruick- 
shank6  in  England  found  croupous  forms  predominant. 
Among  -A3  autopsies  performed  upon  individuals  dead  with 
influenza  Birch-Hirschfeld7  found  11  instances  of  croupous 
lobar  pneumonia,  8  instances  of  croupous  lobular  pneumo- 
nia and  24  instances  of  catarrhal  pneumonia.  Leichten- 
stern thinks  that  the  atypical  symptomatology  of  lobar 
pneumonia  with  influenza — for  example,  the  purulent  char- 
acter of  the  sputum — has  led  many  physicians  to  believe 
that  lobar  pneumonia  rarely  occurs.  It  is  equally  true  that 
many  instances  of  confluent  lobular  pneumonia  are  mis- 
taken for  lobar. 

There  appears  to  be  no  comprehensive  description  of  the 
pneumonias  of  influenza  based  upon  the  epidemics  of  1889- 
i)2.  Descriptions  dating  from  this  period  are  much  ob- 
scured by  attempts  to  separate  croupous  or  fibrinous  from 
catarrhal  pneumonias.  Croupous  lobular  pneumonia  has 
been  recognized,  for  example,  by  Birch-Hirschfeld.  Leicht- 
onstern  describes  a  form  of  pneumonia  which  he  regards  as 


'Leichtenstern,    O. :     Influenza,    Nothnagel's    Specielle    Pathologie    und    Tberapie,    Wien, 

1896,  vol.   ii,  ;it.  2. 
"Krannhals:     Quoted    by    Leichtenstern. 

°Cruickshank:"Brit.    Med.    Jour.,    1S95,    i,    360. 
TBirch-Hirschfeld:      Schmidt's   Jahrbiichcr,    1S90,    ccxxvi,    110. 


PATHOLOGY  AND  BACTERIOLOGY   FOLLOWING   INFLUENZA      111 

neither  lobar  nor  lobular  although  it  implicates  whole 
lobes;  the  consolidated  tissue  is  homogeneous  and  varies 
in  color  from  fleshy  red  to  bluish  red  ;  it  is  tough  arid  elastic 
in  consistency.  The  author  thinks  that  it  is  an  error  to 
regard  this  lesion  as  a  confluent  lobular  pneumonia. 

Kuskow8,  who  has  discussed  the  pathology  of  influenza 
in  considerable  detail,  has  seldom  seen  lobar  pneumonia  but 
has  almost  invariably  found,  even  when  there  is  lobar  dis- 
tribution of  the  lesion,  lobular  patches  of  consolidation  in- 
volving groups  of  lobules,  single  lobules  or  only  parts  of 
lobules;  the  lung  tissue  has  been  hyperemia  and  in  Traces 
edematous. 

Opinions  concerning  the  pathology  and  bacteriology  of 
the  pneumonias  of  influenza,  published  since  the  recent 
epidemic,  have  varied  almost  as  much  as  those  just  cited. 
Few  observers  have  had  the  opportunity  of  making  a  con- 
siderable number  of  observations  under  conditions  which 
determine  the  relation  of  the  pulmonary  lesions  to  the  pri- 
mary disease. 

Keegan9  has  found  with  influenza  a  massive  and  conflu- 
ent bronchopneumonia,  frequently  resembling  lobar  pneu- 
monia but  distinguishable  particularly  in  its  early  stages 
when  the  cut  section  of  the  consolidated  lung  has  a  finely 
granular  character  and  each  bronchiole  stands  out  as  a 
grayish  area  with  intervening  dark  red  alveolar  tissue. 

Symmers10  states  that  the  pneumonia  of  influenza  is  a 
confluent  lobular  exudative  and  hemorrhagic  pneumonia 
which  bears  a  close  resemblance  to  the  pneumonic  variety 
of  bubonic  plague. 

Our  commission11  published  a  preliminary  report  on 
pneumonia  following  influenza  observed  at  Camp  Pike. 
The  occurrence  of  purulent  bronchitis,  distention  of  lungs, 


sKuskow,  N.:     Zur  pathologischen  Anatomie  der  Grippe,  Virchow's  Archiv.,   1S95,   cxxxix, 

406. 
9Keegan,    J.    J..:     The    Prevailing    Epidemic    of    Influenza,    Jour.    Am.    Med.    Assn.,    1918, 

lxxi,    1051. 
10Symmers,    D.:      Pathologic    Similarity    between    Pneumonia  _  of    Bubonic    Plague    and    of 

Pandemic  Influenza,  Jour.   Am.   Med.   Assn.,    1918,  lxxi,    1482. 
"Opie,   E.  L.,   Freeman,  A.   W.,   Blake,   F.   G.,   Small,   J.   C,  Rivers,   T.   M.:     Pneumonia 

Following  Influenza,  Jour.   Am.  Med.  Assn.,   1919,  Ixxii,   536. 


L12      PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATOR'S  TRACT 

peribronchial  hemorrhage  and  bronchiectasis  were  de- 
scribed. I».  influenzae  was  isolated  from  the  bronchi  in  ap- 
proximately s"t  per  cent  of  instances  of  influenzal  pneu- 
monia bul  from  the  consolidated  Lung  in  less  than  half  this 
number  of  autopsies.  Lobar  pneumonia  was  present  in  a 
large  proportion  of  autopsies  bul  was  less  frequent  than 
bronchopneumonia.  Bronchopneumonic  consolidation  is  in 
pari  red,  lobular  and  confluent,  in  part  nodular;  pneumo- 
cocci  have  a  predominant  part  in  the  production  of  these 
Lesions.  Three  types  of  suppurative  pneumonia  are  de- 
scribed: (a)  Abscess  caused  by  hemolytic  streptococci 
usually  in  contact  with  the  pleura  and  accompanied  by  em- 
pyema; {!>)  Suppuration  of  interstitial  tissue  of  the  lung 
caused  by  hemolytic  streptococci  and  accompanied  by  em- 
pyema; (r)  multiple  foci  of  suppuration  clustered  about  a 
bronchus  of  medium  size  and  caused  by  staphylococci.  We 
have  expr<  ssed  the  opinion  that  B.  influenzas  descends  into 
the  bronchi;  pneumococci,  usually  Type  IV,  may  enter  the 
lung  and  produce  either  lobar  or  bronchopneumonia. 
Hemolytic  streptococci  may  descend  and  infect  the  pneu- 
monic lung  causing  death  often  before  suppuration  has  oc- 
curred. Epidemics  of  such  superimposed  streptococcus 
pneumonia  in  wards  of  the  hospital  were  described. 

LeCount12  says:  "The  pneumonia  of  influenza  is  com- 
monly referred  to  as  bronchopneumonia.  It  may  be  so  des- 
ignated, but  it  differs  from  other  bronchopneumonias  in  its 
predilection  Tor  the  periphery  of  the  lungs  and  in  the  extent 
to  which  the  inflammation  is  hemorrhagic. ' ' 

MacCallum13  states  that  the  following  types  of  pneumo- 
nia following  influenza  may  be  recognized.  1.  Pneumococcus 
pneumonia.  The  lobular  character  of  the  consolidation  is 
in  these  cases  well  marked,  although  it  tends  to  lose  its 
definiteness  through  the  confluence  of  adjacent  areas.  The 
cut   surface  of  the  lung  shows  in  the  more  acute  cases  a 


j:LeCount,    V..    R.:     The    Pathological    Anatomy    of    Influenzal    Bronchopneumonia,    jour. 

Am.   Med.    Assn.,    1919,   Ixxii,   6S0. 
"MacCallum,   W.   (",.:     Pathology  "»'  tin-  Pneumonia   Following  Influenza,    four.   Am.   Mid 

Assn.,   1919,  lxxii,   720. 


PATHOLOGY  AND  BACTERIOLOGY    FOLLOWING    I X  I'M  K.VZA     113 

peculiar  lobular  or  confluent  consolidation  which  corre- 
sponds well  with  what  is  commonly  written  of  the  stage 

of  engorgement  in  the  description  of  lobar  pneumonia. 
Later  stages  in  the  pneumonia  show  within  these  areas 
patches  of  rough  gray  consolidated  tissue  from  which  def- 
inite plugs  of  exudate  project.  2.  Staphylococcal  pneumo- 
nia. 3.  Streptococcal  pneumonia.  There  is  lobular  pneu- 
monia, the  interlobular  septa  are  edematous  and,  micro- 
scopically, bronchi  and  alveoli  are  loaded  with  streptococci. 
Whole  areas  of  lung,  though  retaining  their  form,  are  en- 
tirely necrotic.  Lymphatics  are  distended  with  exudate 
containing  streptococci  in  great  numbers,  but  in  none  of 
these  cases  is  interstitial  bronchopneumonia  found.  4. 
Pneumonia  produced  by  B.  influenzae  of  Pf eiffer.  The  lung 
is  studded  with  palpable  shot-like  grayish  yellow  nodules ; 
the  bronchi  exude  thick  yellow  pus,  which  contains  in- 
fluenza bacilli.  Microscopically,  the  walls  of  the  bronchi 
are  found  to  be  thickened  by  mononuclear  infiltration  and 
new  formation  of  connective  tissue.  The  walls  of  the  al- 
veoli are  thickened  and  indurated  and  the  alveoli  often  con- 
tain fibrin  in  process  of  organization.  Absence  of  conspic- 
uous changes  in  lymphatics,  absence  of  intense  pleural  in- 
fection and  relatively  scant  numbers  of  polynuclear  leuco- 
cytes in  the  exudate  within  the  alveoli  and  bronchial  walls 
are,  MacCallum  states,  all  that  distinguish  this  pulmonary 
change  from  the  interstitial  bronchopneumonia  caused  by 
the  hemolytic  streptococcus  and  described  by  him  in 
previous  papers. 

Lyon14  designates  the  pulmonary  lesion  following  in- 
fluenza, hemmorrhagic  pneumonitis,  the  lung  tissue  con- 
taining serous  fluid  loaded  with  red  blood  corpuscles;  in 
many  instances  there  was  such  scant  consolidation  that  the 
process  could  not  be  regarded  as  a  true  pneumonia.  In  35 
instances  the  lesion  was  lobular  in  distribution  and  in  16 


"Lyon,   M.   W.:     Gross  Pathology   of   Epidemic   Influenza  at   Walter   Reed   Hospital,   Toui. 
Am.   Med.   Assn.,    1919,   lxxii,   924. 


114      PNEUMONIAS  AXU   [NFECTIONS  OF   RESPIRATORS  TRACT 

bistances  was  sufficiently  extensive  to  be  designated  Lobar, 
but  it  was  not  typical  lobar  pneumonia,  and.  often  asso- 
ciated with  lobular  patches  of  consolidation,  appeared  t<>  be 
a  confluent  lobular  pneumonia. 

Goodpasture  and  Burnett15  say:  "The  difficulties  of  ana- 
lyzing the  pulmonary  lesions  in  any  group  of  influenza 
pneumonias  as  they  have  appeared  in  this  epidemic,  are 
very  apparent  to  anyone  who  lias  had  an  opportunity  to  ob- 
serve the  bacteriology  and  pathology  of  this  accompani- 
ment of  the  disease."  There  is  an  acute  outflow  of  the 
fluid  elements  of  the  blood  and  of  hemorrhage  into  the  lung 
tissue  filling  the  alveoli  in  lobular  areas  and  not  infre- 
quently in  an  entire  lobe.  By  a  special  method  of  staining 
these  authors  have  studied  the  distribution  of  Gram-nega- 
tive bacilli  with  the  morphology  of  B.  influenzae  The  fact 
that  in  certain  very  early  cases  demonstrable  bacteria  of 
any  kind  are  scarce  or  not  found  at  all,  has  lead  them  to 
believe  "notwithstanding  the  demonstration  of  influenza 
bacilli  in  pure  culture  in  the  lung  in  all  but  one  instance, 
that  at  this  stage  organisms  are  comparatively  few  within 
the  alveoli,  and  the  primary  injury  is  due  to  a  very  potent 
toxic  agent  elaborated  in  and  disseminated. jthrough  the 
larger  air  passages.  In  the  later  stages  or  from  the  be- 
ginning, if  the  injury  be  slight,  the  infection  focalizes  about 
the  bronchi  or  their  terminations,  so  that  the  bronchial  and 
lobular  distribution  becomes  very  conspicuous."  Typical 
lobar  pneumonia  with  "croupous"  exudate  within  the  al- 
veoli occurs  in  cases  complicated  by  secondary  pneumo- 
coccus  infection. 

Wolbach16  has  found  that  two  types  of  pneumonia  are 
characteristic  of  influenza.  In  cases  in  which  death  has 
occurred  within  a  few  days  after  onset  of  pulmonary  signs, 
the  lung  tissue  is  dark  red  and  "meaty  in  consistency"  and 
contains  abundant   blood-tinged   serous   fluid   which   drips 

'^Goodpasture,   E.   W.   ami   Burnett,    F.   T,.:     The   Pathology   of  Pneumonia  Accompanying 

Influenza,  I*.   S.  Naval   Medical   Hull..   1919,  xiii,  No.   J. 
irWoll)ach:     Comments   on    the    Pathology   ami    Bacteriology    of   Fatal    Influenza    Cases   as 

Observed  at  Camp  Devens,  Mass.,  Bull.   Johns    Hopkins  IIosp.   1919,  xxx,   104. 


PATHOLOGY  AND  BACTERIOLOGY    FOLLOWING    I  X  I'l.c  KXZA     115 

from  the  cut  surface.  The  other  type  of  Lesion  is  found  in 
patients  who  have  lived  for  ten  days  or  more  after  onset 
of  the  disease;  there  is  extensive  bronchitis,  bronchopneu- 
monia, discrete  or  confluent,  and  peribronchitis.  The  lungs 
are  voluminous  and  the  smaller  bronchi  are  distended. 
Microscopically,  there  is  peribronchitis  with  extensive  in- 
filtration of  the  interlobular  septa  and  organization  in  al- 
veoli and  bronchioles.  This  lesion  is  that  designated  by 
MacCallum  as  "interstitial  bronchopneumonia."  Wolbach 
thinks  that  the  two  types  of  lesion  represent  different 
stages  of  the  same  process.  He  regards  as  distinctive  of 
the  pneumonias  of  influenza  the  presence  of  hyalin  fibrin 
lining  distended  air  spaces.  With  the  two  types  of  lesion 
which  have  been  described,  B.  influenzae  was  the  only  or- 
ganism which  could  be  cultivated,  and  the  author  associates 
these  distinctive  conditions  with  that  microorganism. 

Streptococcus  Pneumonia. — Finkler  emphasized  the  im- 
portance of  streptococcus  pneumonia  as  a  complication  of 
influenza.  In  1888  he  described  instances  of  acute  primary 
streptococcus  pneumonia  observed  in  1887  and  1889.  This 
form  of  pneumonia,  Finkler  thought,  occurred  in  Bonn  in 
epidemic  form  before  the  influenza  epidemic  of  1889-90 
and,  he  states,  exhibited  an  astonishing  similarity  to  the 
pneumonia  of  influenza.  He  thought  that  later  there  was 
in  Bonn  a  mixed  infection  of  influenza  and  primary  strepto- 
coccus pneumonia.  In  one  type  of  streptococcus  pneumo- 
nia, described  by  Finkler,  there  was  lobular  consolidation 
which  in  multiple  patches  produced  "pseudolobar"  con- 
solidation; the  consolidated  lung  was  smooth  and  red,  and 
similar  to  spleen,  rather  than  hepatized.  In  another  group 
of  instances  the  lesion  merited  the  name  "erysipelas  of 
the  lung."  The  lesion  was  an  acute  interstitial  pneumonia 
in  some  places,  a  cellular  or  occasionally  fibrinous  pneumo- 
nia with  involvement  of  the  interstitial  tissue  in  other 
places.  There  was  edematous  swelling  and  accumulation  of 
leucocvtes  in  the  interstices  between  the  alveoli  and  about 


11(!     PNEUMONIAS  AND  INFECTIONS  OF   RESPIRATOR!    TRACT 

the  blood  vessels  and  bronchi.  Finkler  staled  thai  the  sim- 
ilarity to  erysipelas  mighl  suggesl  thai  the  Lymphatics  con- 
tain streptococci,  bul  this  relation  did  qo1  exist  although 
large  lymphatic  channels  were  occasionally  Tilled  with  coag- 
u In i ) i.  lie  asserted  thai  the  disease  was  contagions  and 
ciied  eases  w  liieli  he  believed  had  their  origin  in  hospital 
wards. 

The  widespread  occurrence  of  streptococcus  pneumonia 
in  the  army  camps  in  this  country  attracted  attention  dur- 
ing the  first  months  of  1018.  Cummings,  Spruit  and 
Lynch17  at  Fort  Sam  Houston,  Texas,  recognized  the  prev- 
alence of  streptococcus  pneumonia,  both  as  a  complication 
of  measles  and  in  association  with  lobar  pneumonia,  and 
showed  thai  the  microorganism  concerned  was  a  hemolytic 
streptococcus.  In  7  autopsies  upon  individuals  with  lobar 
pneumonia,  they  found  pneumococcus  alone  in  2  instances 
and  pneumococcus  and  hemolytic  streptococcus  or  hemo- 
lytic streptococcus  alone  in  5  instances.  Hemolytic  strep- 
tococcus was  found  in  all  of  24  instances  of  bronchopneumo- 
nia, three-fourths  of  which  followed  measles.  They  rec- 
ommend the  bacteriologic  examination  of  the  throat  of 
patients  with  measles  and  the  segregation  of  those  who 
harbor  hemolytic  streptococci. 

Cole  and  MacCallum18  have  published  almost  simul- 
taneously, with  that  just  cited,  a  report  upon  the  pneumonia 
which  has  occurred  at  Fort  Sam  Houston  and  have  shown 
the  importance  of  hemolytic  streptococci  in  its  causation. 
They  have  found  two  varieties  of  pneumonia,  namely,  acute 
lobar  pneumonia  which  does  not  differ  essentially  from 
that  which  occurs  elsewhere  and  bronchopneumonia  which 
in  most  cases  has  followed  measles  and  is  caused  by  S.  hemo- 
lyticus.  They  think  this  infection  is  usually  acquired  in 
the  hospital.  They  believe  that  the  pulmonary  lesions  are 
characteristic.     In  this  publication    and    elsewhere    Mac- 


l7CummingS,  J.  0.,  Spruit,  C.  B,  and  L/vnch,  ('.:  The  Pneumonia-;:  Streptococcus  and 
Pneumococcus   Groups,   Jour.    Am.    Med.   Assn.,    1918,   lxx,    106d. 

1  i  ole,  R.  and  MacCallum,  W.  <i.:  Pneumonia  at  a  Base  Hospital,  Four.  Am  .Med. 
Assn.,    1918,    Ixx,    1146. 


PATHOLOGY  AND  BACTERIOLOGY  FOLLOWING    I  XI'LI   KX/A      117 

Galium  lias  designated  the  lesion  "interstitial  bronchopneu- 
monia. ' ' 

The  epidemic  of  streptococcus  pneumonia  and  empyema 
occurring  at  Camp  Dodge,  Iowa,  from  March  20  to  May  1 0 
is  described  by  Miller  and  Luskiy.  During  this  period  there 
were  400  cases  of  pneumonia,  whereas  from  September  20, 
1917,  to  March  20  there  had  been  only  276  instances  of  lobar 
pneumonia.  The  type  of  pneumonia  changed,  there  was 
more  severe  intoxication  and  empyema  became  very  fre- 
quent ;  in  85  of  95  exudates  streptococci  were  found.  The 
outbreak  of  pneumonia  bore  no  relation  to  measles.  The 
authors  state  that  a  mild  tracheitis  was  prevalent  in  the 
cantonment  during  March,  and  whenever  a  large  group  of 
soldiers  congregated  coughing  was  noticeable. 

MacCallum20  studied  the  pneumonia  at  Camp  Dodge  dur- 
ing May  and  found  17  instances  of  the  lesion  which  he  had 
designated  interstitial  bronchopneumonia;  of  these,  9  fol- 
lowed measles,  although  in  the  earlier  part  of  the  epidemic 
there  appear  to  have  been,  he  states,  few  such  cases.  Cul- 
tures made  at  autopsy,  except  in  a  few  fatal  cases  of  un- 
complicated lobar  pneumonia  caused  by  the  pneumococcus, 
showed  the  hemolytic  streptococcus  in  every  situation 
throughout  the  respiratory  tract  and  pleura. 

The  pneumonia  which  occurred  at  Camp  Funston  is  of 
special  interest  to  our  commission  because  we  were  for  a 
time  stationed  at  this  camp  and  had  the  opportunity  of 
following  in  the  excellent  records  of  the  hospital  the  history 
of  the  occurrence  of  pneumonia  during  the  year  following 
the  establishment  of  the  camp  in  September,  1917.  Stone, 
Phillips  and  Bliss21  have  described  the  outbreak  of  pneu- 
monia which  occurred  in  March,  1918.  At  this  time  there 
was,  the  authors  state,  severe  pneumonia  with  frequent 
empyemas  due  to  hemolytic  streptococci.     This  condition 

1DMiller,  J.  L,.,  and  Eusk,  F.  B.:  Epidemic  of  Streptococcus  Pneumonia  and  Empyema 
at   Camp   Dodge,   Iowa,  Jour.   Am.   Med.   Assn.,    1918,  lxxi,    702. 

MMacCallum,  W.  G.:  Pathology  of  the  Epidemic  of  Streptococcus  Bronchopneumonia 
in  the  Army  Camps,  Jour.  Am.   Med.   Assn.,   1919,   Ixxii,   720. 

:lStone,  W.  J.,  Phillips,  B.  G,  and  Bliss,  W.  P.:  A  Clinical  Study  of  Pneumonia  Based 
on  871   Cases,  Arch.  Int.   Med.,   1918,  xxii,   409. 


118      PNEUMONIAS  AND   INFECTIONS  OF   RESPIRATOR?  TRACT 

which  did  doI  follow  measles  was  responsible  for  the 
greatly  increased  death  rale  in  March;  9  deaths  occurred 
in  February,  45  in  March,  25  in  April  and  14  in  May.  They 
found  during  March  26  instances  of  multiple  pulmonary 
abscess.  In  29  autopsies  they  found  a  pleural  lesion  which 
they  designate  "subcostosternal  pus  pockets";  it  occurs 
only  in  association  with  empyema  caused  by  hemolytic 
streptococci. 

Our  commission--  lias  shown  that  an  epidemic  of  in- 
fluenza, well  characterized  by  its  epidemiology  and  symp- 
toms, preceded  and  accompanied  the  outbreak  of  pneumo- 
nia just  described.  Between  March  4  and  29  1,127  men 
from  Cam])  Funston,  which  then  contained  29,000  men,  were 
sent  to  the  bast1  hospital  with  influenza  and  many  more 
were  treated  in  the  infirmaries  of  the  camp;  on  March  11 
107  patients  with  influenza  were  admitted  to  the  hospital. 
The  greatest  incidence  of  pneumonia  in  the  history  of  the 
encampment  up  to  this  time  occurred  between  .March  9  and 
29,  immediately  following  the  outbreak  of  influenza,  the 
maximum  incidence  of  pneumonia  occurring  five  days  after 
the  maximum  for  influenza. 

The  foregoing  observations  are  cited  to  prove  that  strep- 
tococcus pneumonia,  which  occurred  during  the  spring  of 
1918  at  Camp  Funston  and  doubtless  at  other  camps,  had 
its  origin  in  influenza  and  did  not  differ  in  character  from 
that  which  occurred  on  a  much  larger  scale  in  the  fall  of 
1918. 

Table  of  Autopsies. — In  order  to  present  as  briefly  as 
possible  the  data  upon  which  the  present  study  has  been 
based,  autopsies  have  been  assembled  in  tabular  form  in 
the  order  of  their  performance  (Table  XXVI  I).  During  the 
early  period  of  the  epidemic  autopsies  were  performed  on 
all  who  died  with  pneumonia,  but  later,  with  increase  in  the 
number  of  deaths,  this  became  impossible  and  autopsies 
were  performed  on  all  those  who  died  in  certain  wards. 


--0|,ic.  E.   T...   Freeman.   A.   W..   Blake,   F.   ('■..    Small,   J.   C.   and   Rivers,   T.    M.:     Pneu- 
monia at  Camp   Funston,  Jour.   Am.   Med.   Assn.,    1919,   lxxii,    108. 


PATHOLOGY  AND  BACTERIOLOGY    FOLLOWING    [INFLUENZA      L19 

Comparison  of  charts  representing  incidence  of  influenza 
and  of  deaths  from  pneumonia  furnishes  evidence  that  fa- 
tal pneumonia  during  the  period  of  investigation  was  with 
few  exceptions  referable  to  influenza.  During  two  weeks, 
namely,  from  September  1  to  14,  before  the  presence  of  the 
epidemic  was  evident,  there  were  only  2  fatal  cases  of 
pneumonia.  In  most  instances  the  relation  of  pneumonia 
to  influenza  is  established  by  a  definite  history  of  influenza 
having  its  onset  during  the  epidemic.  Bronchopneumonia 
usually  develops  gradually  as  a  sequence  of  influenza  in 
which  purulent  bronchitis  has  occurred.  Lobar  pneumonia 
may  develop  in  cases  of  influenza  complicated  by  purulent 
bronchitis.  In  some  instances  there  is  apparent  recovery 
from  influenza  indicated  by  return  of  temperature  to  nor- 
mal; after  from  one  to  three  days  of  normal  temperature 
there  is  typical  lobar  pneumonia  with  rusty  sputum.  In 
many  instances  of  pneumonia  having  their  onset  at  the 
height  of  the  epidemic  of  influenza,  the  history  indicates 
that  pneumonia  was  present  immediately  after  the  onset 
of  symptoms,  so  that  the  onset  resembled  that  of  pneu- 
monia rather  than  of  influenza. 

Cases  of  pneumonia  following  measles  have  been  ex- 
cluded from  the  table  in  order  that  they  may  be  studied 
separately  and  compared  with  the  pneumonias  of  influenza. 
It  is  noteworthy  that  the  lesions  of  pneumonia  following 
measles  have  shown  a  very  close  resemblance  to  the  pneu- 
monias of  influenza,  with  regard  both  to  pathologic  char- 
acters and  to  bacteriology. 

Five  instances  of  pneumonia  following  typhoid  fever 
(Autopsies  245  and  329),  scarlet  fever  (Autopsy  311)  or 
mumps  (Autopsies  403  and  417)  have  been  excluded  from 
the  table.  These  secondary  pneumonias  are  grouped  as 
an  appendix  to  the  section  on  pneumonia  following  measles. 
It  is  not  improbable  that  individuals  with  the  diseases 
named    are    just   as    susceptible    as    others    to    influenza. 


120      PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATOR!    TRACT 


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134      PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATORY  TRACT 


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136      PNKr.MoxiAS  AND  [NFECTIONS  OF  RESPIRATOR'S  TRACT 

Included  in  the  table  is  an  instance  (Autopsy  487)  in  which 
a  definite  attack  of  influenza  preceded  scarlet  fever. 

In  successive  columns  the  table  gives  the  autopsy  num- 
ber, race,  and  length  of  military  service.  These  factors 
have  had  an  important  influence  upon  the  incidence  of  in- 
fluenza and  pneumonia  and  have  been  discussed  in  a  pre- 
liminary report.23  The  duration  of  illness  (4tli  column  of 
table),  counted  Prom  the  date  of  onset  of  symptoms  of 
influenza  or  in  some  instances,  when  the  earliest  symptoms 
were  those  of  pneumonia,  from  onset  of  pneumonia,  can 
usually  be  determined  accurately.  The  duration  of  pneu- 
monia (5th  column  of  table)  is  much  more  uncertain,  be- 
cause its  determination  datos  from  the  first  recognition  of 
the  physical  signs  of  pneumonia. 

Clinical  Diagnosis. — The  clinical  diagnosis  recorded 
upon  the  clinical  history  of  the  patient  is  given  in  column  6. 
Many  clinicians  have  been  impressed  with  tho  difficulty 
of  determining  during  life  the  type  of  pneumonia  associated 
with  influenza.  The  occurrence  of  purulent  bronchitis, 
the  frequent  coexistence  of  lobar  and  bronchopneumonia 
and  an  atypical  onset  often  make  the  recognition  of  lobar 
pneumonia  more  difficult  than  usual.  The  diffuse  consoli- 
dation of  confluent  lobular  pneumonia  increases  the  diffi- 
culty of  recognizing  bronchopneumonia.  In  the  table  (col- 
umn 6)  lobar  pneumonia  is  indicated  by  L.,  bronchopneu- 
monia by  B.  Among  227  autopsies  the  clinical  diagnosis 
agreed  with  the  condition  found  at  autopsy  in  109  instances 
(48  per  cent)  ;  in  35  instances  (15.4  per  cent)  both  lobar  and 
bronchopneumonia  were  found  at  autopsy  and  a  diagnosis 
of  one  or  other  was  made  during  life.  In  83  instances 
(36.6  per  cent)  the  diagnosis  made  during  life  was  incor- 
rect. Cases  admitted  to  the  base  hospital  at  Camp  Pike 
were  as  carefully  studied  as  the  conditions  in  a  base  hos- 
pital during  an  epidemic  permitted  and  diagnosis  of  pneu- 
monia was  doubtless  as  accurate  as  in  other  base  hospitals. 


aTour.  Am.   Mid.   Assn.,   1919,  bcxii,  556, 


PATHOLOGY  AND  BACTERIOLOGY  FOLLOWING  INFLUENZA      L37 

Statistics  from  military  and  other  hospitals  based  upon 
clinical  diagnosis  of  the  pneumonias  of  influenza  are  prob- 
ably subject  to  an  error  of  at  least  1  in  ?>  cases,  and  conclu- 
sions based  upon  them  are  almost  valueless. 

The  inaccuracy  of  clinical  diagnosis  of  the  pneumonia 
of  influenza  is  further  illustrated  by  a  consideration  of 
lobar  pneumonia.  This  diagnosis  on  the  one  hand  was 
made  136  times  and  was  correct  67  times  and  incorrect  69 
times ;  on  the  other  hand,  lobar  pneumonia  was  found  at 
autopsy  98  times  and  had  been  diagnosed  in  only  67  of 
these  cases  (68.4  per  cent). 

Classification  of  the  Pulmonary  Lesions  of  Influenza.— 
Influenzal  pneumonia  exhibits  the  following  noteworthy 
characters : 

1.  Acute  bronchitis  with  injury  or  destruction  of  lining 
epithelium  and  accumulation  of  inflammatory  exudate 
within  the  lumen. 

2.  Hemorrhagic  pneumonia  with  accumulation  of  blood 
within  the  alveoli  and  within  and  about  the  bronchi. 

3.  Susceptibilny  of  bronchi  and  pulmonary  tissue  to  sec- 
ondary pyogenic  infection  with  necrosis  and  suppuration. 

4.  Bronchiectasis. 

5.  Tendency  to  the  occurrence  of  chronic  pneumonia  fol- 
lowing failure  of  pneumonia  to  undergo  resolution. 

All  these  changes  are  doubtless  referable  to  the  severity 
of  the  primary  injury  to  the  lower  air  passages. 

In  the  presence  of  destructive  changes  in  the  bronchi 
man}^  bacterial  species,  including  B.  influenza?,  pneumococci 
of  various  types,  streptococci  (notably  hemolytic  strepto- 
cocci) and  staphylococci  may  invade  the  lungs  and  produce 
acute  inflammation.  The  anatomic  characters  of  the  pneu- 
monic lesions  following  influenza  are  equally  varied. 

In  order  to  obtain  insight  into  the  pathogenesis  of  these 
lesions,  it  is  desirable  to  imitate  the  historical  development 
of  knowledge  concerning  the  characters  and  causes  of  dis- 
ease, namely,  first  to  define  accuratelv  the  lesions  concerned 


L38      PNEUMONIAS  AMi   INFECTIONS  OF   RESPIRATORS  TRACT 

and  later  to  determine  with  what  microorganisms  these 
lesions  are  associated.  The  difficulties  of  this  undertaking 
are  increased  by  the  multiplicity  o(  the  microorganisms 
concerned  and  by  the  well-known  truth  that  the  same  mi- 
croorganism, e.  </.,  tht'  tubercle  bacillus,  may  produce 
widely  different  anatomic  lesions. 

In  the  table  of  autopsies  the  following  lesions  are  listed: 

Column  7.  Purulent  bronchitis. — ••!'"  indicates  thai  the  small  bronchi 
contain  mucopurulent  Quid. 

Column  8.  Lobar  pneumonia. — The  occurrence  of  the  lesion  is  indi- 
cated by  the  plus  sign   I    |. 

Column  9.  Peribronchiolar  consolidation. — The  presence  of  nodular 
patches  of  consolidation  about  respiratory  bronchioles  is  indicated  by  the 
plus  sign  (+)  when  the  lesion  lias  been  recognized  at  the  time  of  autopsy. 
When  the  lesion  has  been  first  recognized  by  microscopic  examination  the 
letter  "M"  is  used. 

Column  10.  Hemorrhagic  peribronchiolar  consolidation. — The  occur- 
rence of  this  lesion  which  represents  the  preceding  on  a  background  of 
hemorrhage  is  indicated  by  the  plus  sign  (+). 

Column  11.  Lobular  consolidation. — The  presence  of  the  lesion  is  in- 
dicated by  the  plus  sign  (+). 

Column  12.  Peribronchial  consolidation. — Peribronchial  pneumonia 
recognized  at  the  time  of  autopsy  is  indicated  by  the  plus  sign  (+).  Peri- 
bronchial pneumonia  recognized  microscopically  is  indicated  by  "M."  The 
presence  of  peribronchial  hemorrhage  without  consolidation  is  indicated  by 
"h." 

Column  13.  Abscess  formation  with  pneumonia. — Suppuration  with  ab- 
scess formation  almost  invariably  just  below  the  pleura  is  indicated  by  the 
plus  sign  (+).  Necrosis  of  lung  tissue  recognized  microscopically  and  un- 
accompanied by  suppuration  is  indicated  by  "X." 

Column  14.  Suppurative  interstitial  pneumonia. — This  lesion  invaria- 
bly associated  with  suppurative  lymphangitis  is  indicated  by  the  plus  sign 
(+)• 

Column  15.     Multiple  abscess  in  clusters. — Abscesses  in  clusters  about  a 

bronchus  of  medium   size  are   indicated   by  the  plus  sign    (+). 

Column  16.     Empyema. — The  presence  of  the  lesion  is  indicated  by  "E." 

Column  17.     Bronchiectasis. — "1-5"  indicates  the  lesion. 

Column  18.  Unresolved  bronchopneumonia.— Presence  of  the  lesion  is 
indicated  by  the  plus  sign  (+). 

Column  19.  Organizing"  bronchitis  and  bronchiolitis. — "0"  indicates 
the  lesion. 

The  lesions  of  columns  7  to  12  are  aente  inflammatory 
processes,    columns    9    to    1 12    represent    different    types 


PATHOLOGY  AND   BACTERIOLOGY    FOLLOWING    INFLUENZA      L39 

of  bronchopneumonia.  Columns  13  to  15  represent  sup- 
purative lesions.  Columns  17  to  1!)  represent  chronic 
lesions.  A  survey  of  the  table  shows  the  predominance 
of  acute  lesions  in  the  early  period  of  the  study  and  the 
gradual  increase  of  chronic  lesions. 

The  last  four  columns  of  the  table  of  autopsies  give  the 
bacteriology  of  the  sputum  during  life  and  the  bacteria 
found  in  the  bronchi,  in  the  lungs,  and  in  the  blood  of  the 
heart  after  death. 

Mortality  of  Pneumonia  Following-  Influenza. — From 
September  6  to  December  15,  250  autopsies  were  performed 
on  patients  who  had  died  with  pneumonia  at  the  base  hos- 
pital at  Camp  Pike,  and  with  few  exceptions  bacteriologic 
cultures  were  made  from  them.  Although  it  was  not  pos- 
sible to  perform  autopsies  on  all  who  died,  those  which  were 
performed  afford  a  fair  index  of  all  deaths,  for  throughout 
the  epidemic  of  influenza  and  its  outbreak  of  pneumonia 
approximately  one  half  of  all  who  died  were  examined  after 
death.  The  relation  of  autopsies  to  deaths  is  shown  by  a 
comparison  by  weeks  of  the  number  of  deaths  and  number 
of  autopsies  during  the  months  of  September  and  October. 


"WEEK 

DEATHS 

AUTOPSIES 

Sept.    1-  7 

1 

1 

Sept.    8-14 

1 

1 

Sept.  15-21 

4 

3 

Sept.  22-28 

15 

14 

Sept.  29— Oct.  5 

121 

67 

Oct.      6-12 

191 

78 

Oct.    13-19 

78 

43 

Oct.    20-27 

22 

15 

Oct.    28-31 

8 

6 

441 

228 

For  most  of  these  autopsies  there  is  a  record  of  the 
date  of  onset  of  the  illness,  namely,  influenza,  which  finally 
resulted  in  pneumonia  and  death.  Comparison  of  the  num- 
ber of  cases  of  influenza  which  developed  on  any  day  with 
the  number  of  fatal  cases  which  had  their  onset  on  the  same 


140      PNEUMONIAS  AND  INFECTIONS  OF  RESPIRATOR'S  TRACT 

day  will  determine  the  mortality  of  influenza  at  different 
periods  of  the  epidemic.  Chart  1  shows  the  number  of 
cases  of  influenza  which  had  their  onset  on  each  day  from 
September  1  to  October  31  and  the  number  of  fatal  cases 
with  autopsy  which  had  their  origin  on  corresponding  days. 
The  comparison  by  weeks  between  autopsies  and  total 
number  of  deaths  shows  that  the  autopsies  represent  with 
considerable  accuracy  the  deaths.  Tl*  there  is  any  error  it 
occurs  at  the  height  of  the  outbreak  of  pneumonia  from 
September  29th  to  October  5th  and  not  at  its  beginning, 
or  end.  The  chart  shows  that  the  highest  mortality  occur- 
red among  cases  of  influenza  which  had  their  origin  at  the 
beginning  of  the  epidemic  from  September  _1  to  October  1, 
whereas  after  October  1.  though  the  maximum  number  of 
cases  of  influenza  occurred  on  October  3,  very  few  developed 
fatal  pneumonia. 

Mortality  from  Pneumococcus  and  Streptococcus  Pneu- 
monias.— By  referring  fatal  cases  of  streptococcals  pneu- 
monia back  to  their  date  of  origin  it  is  possible  to  determine 
what  proportion  of  the  cases  of  influenza,  which  developed 
on  any  day,  died  with  infection  by  hemolytic  streptococcals. 
The  accompanying  chart  (Chart  1)  shows  that  infection 
with  hemolytic  streptococci  has  been  very  frequent  at  the 
beginning  of  the  epidemic  of  influenza  (shown  by  area  with 
double  hatch  in  chart)  that  is,  from  September  20  to  30 
and  subsequently  has  gradually  diminished  so  that  few 
cases  have  had  their  onset  in  the  second  half  of  the  epi- 
demic from  September  30  to  October  15. 

Pneumococcus  pneumonia  uncomplicated  by  streptococ- 
cus infection  (shown  by  area  with  single  hatch  in  chart) 
pursued  a  course  which  more  closely  conformed  to  the  curve 
representing  influenza.  The  cases  of  influenza  which  re- 
sulted fatally  bore  a  fairly  constant  ratio  to  the  total  num- 
ber of  cases  of  influenza  from  the  onset  of  the  epidemic 
until  October  1,  but  subsequently  few  cases  of  influenza  de- 
veloped fatal  pneumococcus  pneumonia. 


PATHOLOGY  AND  BACTERIOLOGY    FOLLOWING    IXFLI'LN/A     141 

These  charts  arranged  with  reference  to  the  onset  of  fatal 
pneumonias  dissociate  very  clearly  the  outbreak  of  strep 
tococeus  pneumonia,  which  reached  its  height  at  the  begin- 
ning of  the  influenza  epidemic,  from  the  uncomplicated 
pneumococcus  pneumonia  which  reached  its  maximum  at 
the  midpart  of  the  influenza  epidemic  and  then  abruptly 
abated. 


<■/•£  ■£ 


Chart  1. — Showing  the  relation  of  (a)  onset  of  cases  of  pneumonia  shown  by  autopsy 
to  be  uncomplicated  by  secondary  infection  with  hemolytic  streptococcus,  indicated  by 
upper  continuous  line  with  single  hatch,  and  of  (b)  onset  of  fatal  cases  of  streptococcus 
pneumonia,  indicated  by  the  lower  continuous  line  with  double  hatch,  to  (c)  the  occur- 
rence of  influenza,  indicated  by  the  broken  line.  The  onset  of  each  case  of  fatal  pneu- 
monia is  represented  by  a  single  square. 


Our  study  of  ward  infection  in  pneumonia  furnishes  an 
explanation  of  the  outbreak  of  fatal  streptococcus  pneu- 
monia coincident  with  the  initial  stage  of  the  influenza  epi- 
demic. This  oubreak  is  a  true  epidemic  of  streptococcus 
infection  superimposed,  in  many  instances  at  least,  upon 
preexisting  pneumococcus    pneumonia,    but    in    some    in- 


L42      PNEUMONIAS  AND   [NFECTIONS  OF  RESPIRATOR!'  TRACT 

stances,  doubtless,  a  primary  streptococcus  pneumonia, 
following  the  bronchitis  of  influenza.  In  the  absence  of 
secondary  streptococcus  infection  a  very  large  proportion 
of  these  individuals  would  have  recovered.  This  epidemic 
of  streptococcus  pneumonia,  it  has  been  shown,  was  the  re- 
sull  of  unfavorable  conditions  produced  by  greal  over- 
crowding of  the  hospital  and  in  the  early  pari  of  tin*  epi- 
demic by  inadequate  separation  of  those  with  streptococcus 
infection  from  those  with  none.  Willi  control  of  these  con- 
ditions, streptococcus  pneumonia  rapidly  diminished. 

Greater  susceptibility  to  pneumococcus  pneumonia  in  the 
early  than  in  the  late  period  of  the  epidemic  is  perhaps 
explained  by  differences  in  the  severity  of  influenza;  the 
more  susceptible  individuals  were  attacked  by  influenza 
in  the  early  period,  whereas  the  less  susceptible  did  not 
acquire  the  disease  until  they  had  been  exposed  to  an  im- 
mensely increased  number  of  infected  individuals.  A  bet- 
ter explanation  is  furnished  by  the  greater  opportunity  at 
the  beginning  of  the  epidemic  for  the  transmission  of  mi- 
croorganisms causing  pneumonia,  for  at  this  time  patients 
with  influenza  were  crowded  together  and  methods  to  pre- 
vent the  transmission  of  infection  were  little  used. 

Bronchitis 

Clinical  study  has  shown  that  purulent  bronchitis  (see 
Fig.  2)  occurs  in  about  one-third  of  the  cases  of  influenza. 
In  a  large  proportion  of  cases  of  bronchitis  there  is  no  clin- 
ical evidence  of  pneumonia.  The  bronchial  lesions  found  in 
association  with  the  pneumonia  of  influenza  are  an  index  of 
1  he  ability  of  the  agent,  which  causes  influenza,  to  injure  the 
bronchi. 

Tn  those  who  have  died  with  pneumonia  following  influ- 
enza the  large  bronchi  (with  cartilage)  are  intensely  in- 
jected, so  thai  the  mucosa  has  a  deep  red  color  which 
on  cross  section  contrasts  very  sharply  with  the  pearly 
white  of  the  cartilage.     Superficial  injury  to  the  bronchi  is 


PATHOLOGY  AND  BACTERIOLOGY    FOLLOWING    I  X  I'M  I  KN'ZA      14.'] 

not  infrequently  evident  in  the  larger  bronchial  branches; 
superficial  loss  of  epithelium  is  indicated  by  erosion  of  the 
surface,  whereas  somewhat  deeper  destructive  changes  are 
occasionally  evident.  Microscopic  examination  accurately 
determines  the  degree  of  destructive  change. 

Purulent  bronchitis  was  noted  in  134  autopsies  (55.6  per 
cent  of  autopsies).  From  the  small  bronchi,  in  many  in- 
stances, purulent  fluid  welled  up  upon  the  cut  surface  of 
the  lung,  whereas  in  other  instances  tenacious  mucopuru- 
lent fluid  could  be  squeezed  from  small,  cut  bronchi  by  pres- 
sure upon  lung  tissue.  The  consistency  of  the  material 
within  the  bronchi  varied  greatly,  ranging  from  a  viscid 
and  tenacious  mucus  of  creamy,  yellow  color  to  a  thin,  tur- 
bid, gray  fluid.  The  coexistence  of  local  inflammatory  or 
of  general  edema  of  the  lungs  modifies  the  character  of  the 
material  found  in  the  bronchi  at  autopsy;  with  edema  the 
purulent  exudate  is  in  some  instances  diluted  so  that  a  thin 
cloudy  fluid  flows  from  the  small  bronchi.  In  the  presence 
of  advanced  edema  of  the  lungs  the  bronchi  rarely  if  ever 
contain  purulent  exudate.  The  underlying  changes  in  the 
bronchi  are  more  significant  than  the  character  of  the  exu- 
date found  at  autopsy.  Nevertheless,  the  group  of  cases 
in  which  the  diagnosis  of  purulent  bronchitis  has  been 
made,  because  small  and  medium  sized  bronchi  have  con- 
tained purulent  or  mucopurulent  exudate,  represents  in- 
stances of  readily  recognizable  bronchitis  of  considerable 
severity. 

With  few  exceptions,  purulent  bronchitis  was  diffusely 
distributed  in  the  lungs;  occasionally  it  was  observed  in 
one  lung  alone,  and  in  several  instances  was  limited  to  the 
bronchi  at  the  base  of  a  lung,  usually  of  the  left  lung. 

In  a  considerable  proportion  of  instances  of  purulent 
bronchitis  abnormal  distention  of  the  lungs  was  noted.  On 
removal  from  the  chest  the  lungs  fail  to  collapse  and  retain 
the  size  and  shape  of  the  thorax.  Even  after  section  is 
made  through  the  organ,  parts  of  the  lung  fail  to  collapse 


144     PNEUMONIAS  AND   INl'Kv JTIONS  or-    RESPIRATOR'S  TRACT 

and  have  a  resistanl  cushion-like  consistency.  This  condi- 
tion is  preseni  where  the  lung  tissue  is  air  containing  and 
dry,  and  occurs  when  very  small  bronchi  contain  tenacious 
mucous  exudate  which  becomes  apparent  upon  the  cut  sur- 
face after  the  sectioned  lung  is  squeezed.  Microscopic  ex- 
amination shows  that  the  alveolar  ducts  and  infundibula 
are  distended  with  air,  though  the  respiratory  bronchioles 
contain  inflammatory  exudate.  Complete  obstruction  of 
the  bronchi  is  followed  by  absorption  of  air  from  the  tribu- 
tary pulmonary  tissue  with  atelectasis.  It  is  not  improb- 
able that  partial  obstruction,  permitting  the  penetration  of 
air  with  inspiration,  produces  distention  of  air  containing 
tissue. 

It  is  furthermore  probable  that  cyanosis,  which  is  a  con- 
spicuous feature  of  many  instances  of  pneumonia  following 
influenza,  is  referable,  in  part  at  least,  to  obstruction  of  the 
bronchi  by  mucopurulent  exudate. 

The  term  pneumonia  will  refer  to  those  inflammatory 
changes  in  the  lung  which  are  found  within  the  alveoli;  it 
will  include  inflammatory  changes  in  the  alveoli  surround- 
ing the  respiratory  bronchioles,  in  the  alveolar  ducts  and 
infnndibnla  and  in  their  tributary  alveoli.  Bronchitis  will 
be  described  by  defining  the  changes  which  occur  (a)  in  the 
small  bronchi  with  no  cartilage  or  mucous  glands,  and  (b) 
in  the  large  bronchi  including  the  primary  branches  of  the 
trachea. 

For  convenience  of  description  those  bronchi  may  bo 
designated  small,  which  have  no  cartilaginous  plates  in 
their  wall.  Larger  bronchi  have  cartilage  and  mucous 
glands,  the  latter  situated  in  considerable  part  outside  the 
cartilaginous  plates.  These  bronchi,  of  which  the  largest 
are  the  right  and  left  bronchi  formed  by  bifurcation  of  the 
trachea,  diminish  with  repeated  branching  to  a  caliber  of 
about  1  mm.  Small  bronchi  are  lined  by  columnar  ciliated 
epithelium;  their  Avail  consists  of  very  vascular  connective 


PATHOLOGY  AND    l5A(!TI<:i;iOU><;V    FOLLOWING    I  N  KM  '  KX/A      145 

tissue  containing  a  layer  of  smooth  muscle  and  their  cali- 
ber varies  approximately  from  1  to  0.5  mm.  It  is  con- 
venient to  designate  as  respiratory  bronchioles24  the  ter- 
minal ramifications  of  the  bronchi;  they  are  lined  by  a 
single  layer  of  columnar  ciliated  cells  passing  over  into 
cuboidal  nonciliated  epithelium  and  are  beset  with  small 
air  sacs  lined  by  flat  cells  or  epithelial  plates  similar  to  those 
of  the  alveoli  elsewhere.  Not  infrequently  these  alveoli  oc- 
cur along  only  one  side  of  the  bronchiole,  the  remainder  of 
the  circumference  being  covered  by  a  continuous  layer  of 
cubical  epithelium.  The  respiratory  bronchiole  by  branch- 
ing along  its  course  or  at  its  end  is  continued  into  several 
alveolar  ducts  which  unlike  the  respiratory  bronchioles 
have  no  cubical  or  columnar  epithelium  but  are  closely  be- 
set by  alveoli  lined  by  flat  epithelial  plates.  The  alveolar 
duct  is  recognized  by  the  absence  of  cubical  epithelium  and 
the  presence  of  bundles  of  smooth  muscle  which  occur  in 
the  wall.  The  infundibula  or  alveolar  sacs  arise  as 
branches  from  the  alveolar  ducts  and  like  them  are  beset 
with  alveoli,  but  smooth  muscle  does  not  occur  in  their 
walls.  The  base  of  the  infundibulum  is  wider  than  its  ori- 
fice, which  Miller  states  is  surrounded  by  a  sphincter-like 
bundle  of  smooth  muscle. 

Changes  in  the  main  bronchi  and  their  primary  branches 
are  usually  less  severe  than  those  in  bronchi  of  smaller 
size.  The  epithelium  is  often  intact,  the  superficial  cells 
being  columnar  and  ciliated,  but  not  infrequently  des- 
quamation of  superficial  cells  has  occurred  and  the  lower 
layers  alone  remain.  Occasionally  (Autopsy  471)  there  is 
necrosis  of  epithelium  with  which,  although  the  architec- 
ture of  cells  is  preserved,  nuclei  have  disappeared.  Accu- 
mulation of  blood  or  serum  may  separate  epithelium  from 
the  underlying  basement  membrane  (Fig.  1).  Complete 
loss  of  epithelium  occurs,  usually  in  small  patches. 

24Mil1er,    VV.    S.:     Am.    Rev.   Tuberc,    1919,    Hi,    65. 


14l!      PNEUMONIAS  AX1'   INFECTIONS  OF  RESPIRATOR?  TRACT 

Polynuclear  leucocytes  are  numerous  upon  the  surface 
of  the  epithelium  and  are  sometimes  fixed  in  process  of 
migration  through  epithelium  and  basement  membrane. 

The  blood  vessels  of  the  mucosa  are  engorged.  There 
is  sometimes  edema  or  hemorrhage,  and  in  the  superficial 
part  of  the  mucosa  polynuclear  leucocytes  are  often  fairly 
abundant.  When  superficial  epithelium  has  been  lost,  poly- 
nuclears  arc  numerous  immediately  below  the  surface  of 


Fig.    1. — Acute   bronchitis   showing  engorgement   of  blood   vessels  of  mucosa  and   elevation 
of  epithelium   by   serum   and   blood.     Autopsy    3r>2. 

the  exposed  tissue.  Fibrin  is  often  present  upon  the  de- 
nuded surface  and  extends  for  a  short  distance  into  the 
tissue  below.  In  the  deeper  part  of  the  mucosa,  about  the 
muscularis  and  especially  about  and  between  the  acini  of 
the  mucous  glands,  the  tissue  is  infiltrated  with  lymphoid 
and  plasma,  cells. 

Changes  in  the  mucous  glands  are  invariably  present. 
These  changes  are  distention  of  ducts  and  acini  with  mu- 


PATHOLOGY  AND  BACTERIOLOGY    FOLLOWING    I NTL1  KXZA     147 

cons,  degenerative  changes  occasionally  ending  in  necrosis 
of  cells,  disappearance  of  acini,  dense  infiltration  of  inter- 
stitial tissue  with  lymphoid  and  plasma  cells  and  finally 
proliferation  of  this  interstitial  tissue.  The  duet  of  a  mu- 
cous gland,  dilated  and  filled  with  mucus,  may  be  sur- 
rounded by  lymphoid  and  plasma  cells  in  great  number. 
Acini,  similarly  dilated,  contain  mucus  and  are  composed  of 
cubical  cells  which  have  discharged  their  mucous  content. 
In  some  instances  (e.  g.,  Autopsy  257)  the  cells  of  the  acini 
have  undergone  necrosis;  the  cytoplasm  stains  homogen- 
eously and  the  nuclei  have  disappeared.  Where  necrosis 
has  occurred,  polynuclear  leucocytes  may  penetrate  into 
the  dead  cells.  In  association  with  degenerative  changes 
in  the  acini  there  is  abundant  infiltration  of  the  interstitial 
tissue  within  and  about  the  glands  with  lymphoid  and 
plasma  cells.  When  the  acini  have  disappeared  there  is 
proliferation  of  fibroblasts  and  new  formation  of  fibrous 
tissue,  and  mucous  glands  are  found  in  which  a  few 
atrophied  acini  are  separated  by  newly  formed  fibrous 
tissue. 

With  the  bronchitis  of  influenza  the  small  bronchi  (with 
no  cartilage  or  mucous  glands)  show  every  stage  of  transi- 
tion from  early  acute  inflammation  characterized  by  accu- 
mulation of  polynuclear  leucocytes  within  the  lumen,  en- 
gorgement of  blood  vessels,  and  infiltration  of  the  wall  with 
polynuclear  leucocytes,  through  various  stages  of  destruc- 
tive changes  to  complete  disappearance  of  the  bronchial 
wall  and  formation  of  an  abscess  cavity  at  the  site  of  the 
bronchus.  In  the  early  stages  of  acute  bronchitis,  hemor- 
rhage is  frequently  associated  with  the  lesion.  Blood  may 
be  abundant  within  the  lumen  of  the  bronchus,  and  in  the 
mucosa  red  blood  corpuscles  often  infiltrate  the  tissue 
around  greatly  distended  blood  vessels,  or  accumulating 
below  the  epithelium,  separate  it  from  its  basement  mem- 
brane. Hemorrhage  is  not  limited  to  the  wall  of  the  bron- 
chus, but  frequently  occurs  into  the  alveoli  in  a  zone  en- 
circling the  bronchus. 


14S      PNEUMONIAS  AND   [NFECTIONS  OF  RESPIRATOR'S  TRACT 

With  acute  bronchitis  there  may  be  desquamation  of 
epithelial  cells  with  partial  or  complete  loss  of  epithelial 
lining.  In  the  smallest  bronchi  the  single  layer  of  colum- 
nar cells  may  be  separated  in  places  from  the  underlying 

tissue,  so  that  intact  rows  of  cells  are  round  within  the 
lumen.  Tn  somewhat  larger  bronchi,  lined  by  epithelium 
in  multiple  layers,  superficial  columnar  ciliated  cells  may 
be  lost.  In  some  instances  superficial  epithelial  cells  ap- 
pear to  have  lost  their  cohesion  and  are  separated  by  nar- 
row spaces:  in  these  instances,  polynuclear  leucocytes  are 
often  numerous  between  epithelial  cells.  Epithelium  is  oc- 
casionally separated  from  its  basement  membrane  by  small 
accumulations  of  serum  or  blood.  Occasionally  necrosis 
of  epithelial  cells  with  disappearance1  of  nuclei  is  seen  and 
is  doubtless  caused  by  the  action  of  bacteria;  the  affected 
cells  may  be  raised  from  the  underlying  tissue  by  accu- 
mulated serum  (Autopsy  253).  The  changes  which  have 
been  described  bring-  about  partial  or  complete  loss  of 
the  ciliated  lining  of  the  bronchial  tube. 

The  severity  of  changes  in  the  bronchial  wall  is  in  direct 
relation  to  the  extent  of  destruction  of  the  lining  epi- 
thelium :  when  the  epithelium  remains  intact  polynuclear 
leucocytes  may  be  found  in  considerable  number  imme- 
diately below  it,  but  as  the  lesion  progresses,  cells  in  great 
part  mononuclear,  namely,  lymphoid  and  plasma  cells,  ac- 
cumulate in  large  number  throughout  the  wall  of  the  bron- 
chus. There  is  often  abundant  cellular  infiltration  within 
and  about  the  bundles  of  the  muscular  coat.  The  changes 
assume  the  character  of  chronic  inflammation. 

When  the  lining  epithelium  of  the  bronchus  is  lost,  fibrin 
tends  to  accumulate  over  the  surface  of  the  defect,  to  which 
it  is  firmly  attached.  It  remains  separated  by  a  conspicu- 
ous space  from  adjacent  intact  epithelium  over  which  it 
may  project.  This  superficial  network  of  fibrin  merges 
with  a  similar  network,  extending  to  a  variable  depth  within 
the  tissue.     "What  mav  well   be   described   as  coagulative 


PATHOLOGY  AND  BACTERIOLOGY  FOLLOWING  INFLUENZA     149 

necrosis  has  often  occurred,  and  structures,  such  as  white 
fibrous  bundles  or  wall  of  blood  vessels,  are  marked  out 
by  hyaline  material  which  merges  with  fibrin.  When  the 
walls  of  the  blood  vessels  which  are  invariably  engorged 
are  involved,  the  lumen  is  plugged  by  a  fibrinous  thrombus. 

Little  patches  of  fibrin  adherent  to  the  inner  surface  of 
the  bronchus  may  occur  in  spots  where  epithelium  has  been 
lost ;  with  uniform  loss  of  epithelium  the  entire  circumfer- 
ence may  be  lined  with  fibrin  forming  a  circular  zone 
occasionally  quite  uniform  in  thickness. 

Accumulations  of  polynuclear  leucocytes  doubtless  bring 
about  conditions  which  cause  solution  of  fibrin  or  prevent 
its  formation  (when  disintegration  of  leucocytes  sets  free 
leucoprotease  in  abundance).  The  activity  of  the  infecting 
microorganisms,  usually  hemolytic  streptococci  or  staphylo- 
cocci, may  cause  complete  necrosis  of  a  part  or  all  of  the 
bronchial  wall.  The  cavity  which  is  formed  may  penetrate 
into  lung  tissue  that  has  previously  undergone  pneumonic 
consolidation. 

Further  changes  caused  by  the  bronchitis  of  influenza 
will  be  considered  under  peribronchial  hemorrhage  and 
edema,  peribronchial  pneumonia  and  bronchiogenic  ab- 
scess. Purulent  bronchitis  is  almost  invariably  associated 
with  dilatation  of  the  bronchi,  the  affected  bronchi  being- 
distended  with  pus.  With  increasing  dilatation  bronchiec- 
tasis becomes  evident  upon  gross  examination  of  the  tissue, 
and  is  much  more  advanced  in  the  small  bronchi  than  in 
the  larger  cartilaginous  passages.  This  subject  will  be 
further  considered  under  bronchiectasis. 

In  association  with  the  acute  bronchitis  of  influenza  the 
epithelium  of  bronchi  not  infrequently  looses  its  superficial 
columnar  ciliated  cells  and  assumes  some  of  the  characters 
of  a  squamous  epithelium  being  covered  by  polygonal  or 
flat  cells  (Figs.  17  and  18).  The  condition  is  often  de- 
scribed a  "squamous  metaplasia,"  although  it  doubtless 
represents  a  stage  of  regeneration  following  injury  rather 


150      PNEUMONIAS   AND   INFECTIONS  OF   RESPIRATORY  TRACT 

than  a  true  metaplasia.  The  basal  cells  of  the  epithelium 
have  a  cubical  or  columnar  form;  above  them  the  cells  be- 
come polygonal  and  as  the  surface  is  approached,  cells  are 
Mat  and  even  scale-like.  The  nuclei  of  these  superficial 
cells  are  often  lost.  There  is  no  close  resemblance  to  the 
squamous  epithelium  of  the  skin,  for  intercellular  bridges 
are  not  seen. 

This  change  may  occur  within  six  days  after  onset  of 
influenza,  though  in  most  instances  the  duration  of  illness 
lias  been  two  weeks  or  more.  It  may  affect  either  large 
or  small  bronchi,  but  it  is  more  frequently  found  in  the 
latter.  Whenever  ciliated  columnar  cells  are  lost,  super- 
ficial cells  tend  to  become  fiat.  Epithelium  on  one  side  of  a 
bronchus  may  have  a  squamous  character,  whereas  that 
elsewhere  is  columnar  and  ciliated.  The  flat  epithelium  may 
undergo  thickening  so  that  it  is  0.1  mm.  or  more  in  thick- 
ness. It  is  noteworthy  that  regenerating  epithelium  grow- 
ing over  a  denuded  surface  has  the  squamous  character 
which  has  been  described  (Plate  XIV,  Fig.  22). 

Bacteriology  of  the  Bronchitis  of  Influenza. — With  the 
pneumonia  of  influenza,  bronchitis  is  invariably  present. 
Cultures  have  been  made  from  the  right  or  left  main  bron- 
chus or  from  the  very  small  bronchi  which  contained  puru- 
lent exudate.  A  routine  method  of  making  the  culture  has 
been  adopted.  The  right  main  bronchus,  exposed  by  draw- 
ing the  right  lung  out  of  the  chest  and  toward  the  midline, 
was  widely  seared  with  a  hot  knife;  the  bronchus  was  par- 
tially cut  across  through  the  seared  surface  with  a  heated 
knife  and  a  platinum  needle  inserted  into  the  lumen.  The 
bacteria  obtained  named  in  the  approximate  order  of  their 
relative  frequency  have  been:  ]>.  influenza1,  pneumococci, 
hemolytic  streptococci,  staphylococci  (aureus  and  albus), 
B.  coli,  S.  viridans,  M.  catarrhalis,  and  diphthoid  bacilli 
which  have  not  been  identified.  Mixed  infections  occurred 
in  most  instances.     The  following  list  arranged  by  grouping 


PATHOLOGY  AND  BACTERIOLOGY    FOLLOWING   INFLUENZA      1  5  1 

bacteria  in  the  order  cited  above,  shows  how  varied  have 
been  the  combinations  which  occur: 

B.  influenzae   .'; 

Pneumococci    5 

S.    hemolyticus    3 

Staphylococci     '.', 

B.  coli 3 

S.  viridans   1 

B.  influenzae,  pneumococci    17 

B.   influenzae,    S.   hemolyticus    18 

B.    influenzae,    staphylococci 4 

Pneumococci,  S.  hemolyticus   1 

Pneumococci,   staphylococci    3 

S.    hemolyticus,    staphylococci 4 

S.  hemolyticus,  B.  coli 2 

Staphylococci,   S.   viridans 1 

B.  influenzae,  pneumococci,  S.  hemolyticus   6 

B.  influenzae,  pneumococci,  staphylococci 15 

B.  influenzae,  pneumococci,  S.  viridans 2 

B.  influenzae,  S.  hemolyticus,  staphylococci 16 

B.  influenzae,  S.  hemolyticus,  M.  catarrhalis 1 

B.  influenzas,  staphylococci,   S.  viridans 1 

Pneumococci,  S.  hemolyticus,  staphylococci 3 

Staphylococci,  B.  coli,  S.  viridans   1 

B.  influenzas,  pneumococci,  S.  hemolyticus,  staphylococci 7 

B.  influenzae,  pneumococci,  staphylococci,  M.  catarrhalis 1 

B.  influenzae,  S.  hemolyticus,  staphylococci,  B.  coli 1 

B.  influenzae,  S.  hemolyticus,  staphylococci,  S.  viridans 1 

B.  influenzae,  S.  hemolyticus,  staphylococci,  M.  catarrhalis 1 

B.  influenzae,  staphylococci,  S.  viridans,  M.  catarrhalis 1 

B.  influenzae  has  been  present  in  the  bronchi  in  79.3  per 
cent  of  instances  of  pneumonia  referable  to  influenza.  Com- 
binations which  have  been  found  most  frequently  are  B. 
influenza?  and  pneumococci  (17  instances),  B.  influenzae  and 
hemolytic  streptococci  (18  instances),  or  the  same  combina- 
tions with  staphylococci,  namely,  B.  influenzae,  pneumococci 
and  staphylococci  (15  instances),  and  B.  influenzae,  hemo- 
lytic streptococci  and  staphylococci  (16  instances).  There 
is  little  doubt  that  B.  influenzae  was  not  identified  in  some 
instances  in  which  it  was  present ;  when  other  microorgan- 
isms are  very  numerous  its  inconspicuous  colonies  may  be 
overgrown  even  though  the  presence  of  pneumococci,  strep- 


152      PNEUMONIAS  AND  [NFECTIONS  OF  RESPIRATOR!?  TRACT 


tococci  or  staphylococci  tends  to  increase  the  size  of  its  col- 
onics. Moreover,  it  is  not  improbable  thai  the  microorgan- 
ism may  disappear  Prom  the  bronchi.  Comparison  with 
observations  made  upon  influenza  suggests  that  multiple 
methods  of  examination  mighl  have  demonstrated  a  much 
higher  incidence  of  B.  influenza?.  Throat  cultures  alone 
made  during  life  demonstrated  the  presence  of  B.  influenza" 
in  only  65.7  per  cent  of  patients  with  acute  influenza, 
whereas  when  cultures  were  made  from  the  nose,  throat 
and  sputum,  and  a  mouse  was  inoculated  with  sputum  from 
each  patient,  B.  influenza1  was  found  in  every  instance. 
After  the  acute  stage  of  the  disease  had  passed,  the  num- 
ber of  microorganisms  diminished,  and  in  many  instances 
I),  influenzae  disappeared  from  the  upper  air  passages.  In 
some  of  our  autopsies  B.  influenzae  doubtless  present  dur- 
ing life  has  similarly  disappeared  before  death  due  to 
pneumonia  caused  by  pneumococci  or  streptococci.  In  view 
of  these  considerations  it  is  not  improbable  that  B.  iuflu- 
enzse  demonstrated  by  a  single  culture  in  80  per  cent  of 
instances  has  been  constantly  present. 

Table  XXVIII  represents  the  incidence  of  pneumococci, 
hemolytic  streptococci,  staphylococci,  and  B.  influenza'  in 
the  bronchi,  lungs  and  blood  of  those  individuals  with  pneu- 
monia in  whom  baeteriologic  examination  has  been  made  at 
autopsy.  The  number  of  cultures  made  from  the  bronchi, 
lungs  or  blood  of  the  heart  is  given  in  the  second  column 
of  the  table  and  in  other  columns  are  given  the  incidence  in 
number  and  percentage  of  the  microorganisms  which  have 
been  mentioned. 

Table   XXVIII 


■   - 

I'XEFMOCOCCl 

HEMOLYTIC 
STREPTOCOCCI 

STAPHYLO- 
COCCI 

B.  INFLU- 
ENZAE 

> 

O   o 
£    ft. 

(3    W 

S  c 
ft.  6. 

> 
Z  ft. 

Be 

O    E- 

B2    "/. 

fcj    O 
6.    ft. 

H 

•  7. 

O    o 

y.  p., 

H    O 

ft.    ft. 

Eh 

pi 

y.  cu 

w  £ 

O    E-. 

sa  w 
W  o 

a.  ft. 

Bronchus 

Lung 

Blood 

121 

l.-,:; 
218 

56 
68 

87 

46.?, 
44.4 
39.9 

58 

77 
85 

47.9 
50.3 
39.0 

61 

37 

1 

50.4 

24.2 

0.5 

96 

70 
1 

79.3 

45.7 

0.5 

PATHOLOGY  AND  BACTERIOLOGY  FOLLOWING  INFLUENZA     153 

Cultures  from  the  bronchus  represent  the  bacteriology 
of  the  bronchitis  of  influenza.  Infection  of  the  Lung  fol- 
lowing influenza  doubtless  occurs  by  way  of  the  bronchi, 
so  that  the  bacteria  which  cause  pneumonia  are  present  in 
the  bronchi  before  they  enter  the  lung  tissue.  The  figures 
in  Table  XXVIII,  similar  to  those  previously  cited,  show 
the  high  incidence  of  B.  influenzae,  and  the  occurrence  of 
pneumococci,  hemolytic  streptococci  and  staphylococci  each 
present  in  approximately  half  of  all  autopsies. 

The  figures  in  Table  XXVIII  are  an  index  of  the  capacity 
of  the  microorganisms  which  enter  the  bronchi  to  invade 
the  lungs  and  finally  the  blood.  Pneumococci  were  pres- 
ent in  the  bronchi  in  46.3  per  cent  of  instances,  in  the  lungs 
in  only  slightly  less,  and  in  approximately  40  per  cent  of 
autopsies  they  had  penetrated  into  the  blood.  Hemolytic 
streptococci  enter  the  bronchi  with  the  same  frequency  and 
exhibit  an  equal  ability  to  penetrate  into  the  lungs  and 
blood.  Staphylococci  enter  the  bronchi  in  half  of  these  in- 
dividuals, but  penetrate  into  the  lungs  in  only  a  fourth  of 
the  instances.  They  have  entered  the  blood  only  once  (Au- 
topsy 263)  in  this  instance  in  association  with  hemolytic 
streptococci.  B.  influenzae  has  been  present  in  the  bronchi 
in  approximately  80  per  cent  of  autopsies.  It  is  notewor- 
thy that  it  has  been  found  in  the  lung  in  little  more  than 
half  this  percentage  of  instances  and  has  entered  the  blood 
only  once  (Autopsy  474),  in  this  instance  in  association  with 
hemolytic  streptococci. 

In  a  limited  number  of  autopsies  there  was  purulent 
bronchitis  recognized  by  the  presence  of  mucopurulent  ex- 
udate in  small  bronchi.  It  has  been  stated  that  this  group 
of  cases  is  not  sharply  separable  from  other  instances  of 
bronchitis,  because  in  some  cases  death  has  occurred  before 
a  purulent  exudate  has  accumulated  or  in  other  instances 
a  purulent  exudate  has  been  disjriaced  by  edema.  Table 
XXIX  shows  the  bacteriology  of  instances  of  purulent 
bronchitis : 


154      PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATORS   TRACT 


Table  X  X  1  X 


s. 

K 

:  - 

z  o 

Bronchus 

66 

i-M  iMOcoeci 


w 

> 

H 

O   E* 

c^ 

a  x 

6 

O 

w  o 

:-". 

s. 

-  - 

33 


50.0 


HEMOLYTIC 
STREPTOCOCCI 


K 

> 

H 

O    Eh 

•    M 

a  i. 

O    o 

u;  o 

X.    ft. 

a.  ft. 

32 


48.5 


STAPH!  I.o- 
.  (KVI 


p  6 


36 


54.5 


B.  iM'i.r- 
enz^: 


o  6 

V.    ft. 


53 


80.3 


The  percentages  of  various  bacteria  with  purulent  bron- 
chitis do  not  differ  essentially  from  those  obtained  from 
all  autopsies  with  pneumonia.  B.  influenzae  is  found  in  ap- 
proximately 80  per  cent  of  autopsies.  In  16  instances  cul- 
tures were  made  Prom  the  purulent  fluid  contained  in  a 
small  bronchus  and  the  incidence  of  B.  influenza1  (namely, 
81.4  per  cent)  has  not  differed  from  that  in  the  main  bron- 
chus. In  7  of  8  instances  in  which  cultures  were  made,  both 
from  the  right  main  bronchus  and  from  the  purulent  fluid 
in  a  small  bronchus,  B.  influenza1  was  found  in  one  or  other 
in  all  but  one  autopsy  (87.5  per  cent)  ;  in  this  instance  (Au- 
topsy 472)  respiratory  disease  began  thirty-seven  days  be- 
fore death  and  cultures  from  large  and  small  bronchi  at 
autopsy  were  overgrown  by  B.  coli.  Since  observations 
upon  influenza  made  during  life  have  shown  that  B.  influ- 
enza? is  constantly  demonstrable  when  multiple  methods  are 
employed  for  its  detection,  the  figures  just  cited  give  sup- 
port to  the  suggestion  that  B.  influenzae  is  constantly  pres- 
ent in  the  bronchi  with  the  bronchitis  of  influenza. 


Lobar  Pneumonia 

The  frequency  with  which  the  confluent  lobular  consol- 
idation of  bronchopneumonia  involving  whole  lobes  or 
parts  of  lobes  follows  influenza  has  emphasized  the  desira- 
bility of  distinguishing  carefully  between  lobar  and  conflu- 
ent lobular  pneumonia.  The  pulmonary  lesion  has  been 
designated  lobar  pneumonia  when  it  exhibited  the  well- 
known  characters  of  this  lesion,  namely,  firm  consolidation 
of  large  parts  of  lobes,  coarse  granulation  of  the  cut  sur- 


PATHOLOGY  AND  BACTERIOLOGY  FOLLOWING  I  X  I'LT  KXXA   L55 

face,  fibrinous  plugs  in  the  bronchi  and,  on  microscopic  ex- 
amination, homogeneous  consolidation  and  fibrinous  plug- 
within  the  alveoli.  With  confluent  lobular  consolidation  of* 
bronchopneumonia  the  consolidated  area  is  in  most  cases 
obviously  limited  by  lobule  boundaries,  and  well-defined 
lobules  of  consolidation  occur  elsewhere  in  the  lungs. 

Lobar  pneumonia  occurred  in  98  among  241  instances  of 
pneumonia  following  influenza,  namely,  in  40.7  per  cent  of 
autopsies. 

The  difficulty  of  separating  lobar  and  bronchopneumonia 
following  influenza  has  been  increased  by  the  frequent  com- 
bination of  the  two  lesions  in  the  same  individual.  There 
were  34  instances  in  which  lobar  and  bronchopneumonia 
occurred  together.  The  anatomic  diagnosis  of  lobar  pneu- 
monia was  made  only  when  lobes  or  parts  of  lobes  were 
firmly  consolidated  and  exhibited  the  characters  of  the  le- 
sion enumerated  above ;  in  several  instances,  in  which  there 
was  some  doubt  concerning  the  nature  of  the  lesion,  micro- 
scopic examination  was  decisive.  The  associated  broncho- 
pneumonic  lesions  represented  all  the  types  which  have 
been  associated  with  influenza.  In  the  group  of  34  cases  of 
coexisting  lobar  and  bronchopneumonia,  lobular  consolida- 
tion occurred  10  times,  peribronchiolar  consolidation  14 
times  (recognized  in  all  but  4  instances  by  microscopic  ex- 
amination), hemorrhagic  peribronchiolar  consolidation  9 
times,  peribronchial  pneumonia  4  times.  The  intimate  re- 
lation of  these  lesions  to  changes  in  the  bronchi  is  well 
shown  by  the  frequent  presence  of  purulent  bronchitis. 
The  associated  lesions  of  the  bronchi  in  these  cases  were  as 
follows :  purulent  bronchitis  in  23  instances ;  peribronchial 
hemorrhage  in  6;  bronchiectasis  in  11.  The  frequency  of 
purulent  bronchitis  and  other  bronchial  lesions  in  associa- 
tion with  coexisting  lobar  and  bronchopneumonia  is  in 
sharp  contrast  with  the  occurrence  of  these  lesions  in  asso- 
ciation with  lobar  pneumonia  alone;  with  69  instances  of 


151 


)      PNEUMONIAS  AN1>    INFECTIONS  OF   RESPIRATOR'S   TRACT 


Lobar  pneumonia  alone  purulenl   bronchitis    occurred    17 
times  and  bronchiectasis  once. 

Lobar  pneumonia  following  influenza  passes  through  the 
usual  stages  of  red  and  gray  hepatization.  Red  hepatiza- 
tion was  found  l(i  times,  combined  red  and  gray  hepatiza- 
tion 28  times,  and  gray  hepatization  20  times.  The  average 
duration  of  pneumonia  with  red  hepatization  was  3.7  days, 
with  combined  red  and  gray  hepatization  5.1  days  and  with 
gray  hepatization  7..")  days.  These  figures,  it  will  be  shown 
later,  have  seme  importance  in  relation  to  the  stage  at 
which  hemolytic  streptococcus  infects  lungs  the  site  of 
lobar  pneumonia. 

Bacteriology  of  Lobar  Pneumonia. — Table  XXX  is  com- 
piled with  the  purpose  of  determining  the  bacteriology 
of  the  bronchi,  lungs  and  heart's  blood  in  autopsies 
performed  on  individuals  with  lobar  pneumonia.  In  some 
instances  bacteriologic  examination  of  one  or  other  of  these 
organs  was  omitted;  the  percentage  incidence  is  an  index 
of  the  presence  of  pneumococci,  hemolytic  streptococci, 
staphylococci  or  B.  influenza1  in  the  bronchi,  lungs  or 
heart's  blood  and  measures  the  invasive  power  of  these  mi- 
croorganisms during  the  course  of  lobar  pneumonia  fol- 
lowing influenza. 

Table  XXX 


PNEUMOCOCCI 

HEMOLYTIC 

STAPHYLO- 

B. INFLU- 

6. s 

=  1 

6  _ 

V.  o 

STREPTOCOCCI 

COCCI 

ENZAE 

£ 

A  S3 

s  ° 

£    ft. 

°    £ 

fiS    53 

a  o 

ft.    ft. 

B 

jH 

ri     53 

s  ° 

&5 

°  £ 

s  55 

K    O 
ft,    ft. 

g 

a  S3 

p    o 

85 

ti   r. 

K    O 

6-    ft. 

g 

^  S3 

P  0 

>5   ft. 

BE 

a  0 

a.  ft. 

Bronchus 

44 

29 

56.9 

14 

31.8 

22 

50.0 

37 

84.1 

Lung 

53 

41 

77.3 

13 

24.5 

8 

15.1 

26 

49.1 

Blood 

87 

57 

(i.1.5 

11 

12.6 

Pneumococci,  the  recognized  cause  of  lobar  pneumonia, 
were  found  in  the  lungs  in  73.3  per  cent  of  autopsies;  fail- 
ure to  find  the  microorganism  in  all  instances  is  doubtless 
the  result  of  its  disappearance  from  the  lung,  which,  it  is 
well  known,   occurs   not   infrequently   particularly  during 


PATHOLOGY  AND  BACTERIOLOGY   FOLLOWING   [NFLUENZA     157 

the  later  stages  of  the  disease.    In  65.5  per  cent  of  instances 
of  fatal  lobar  pneumonia   pneumococci   have  entered  the 

heart's  blood. 

Hemolytic  streptococci  unlike  pneumococci  were  found 
more  frequently  in  the  bronchi  than  in  the  lungs;  this  mi- 
croorganism which  exhibits  little  tendency  to  disappear, 
once  it  has  established  itself  within  the  body,  found  en- 
trance into  the  bronchi  in  31.S  per  cent  of  instances  of  lobar 
pneumonia  and  in  24.5  per  cent  entered  the  lungs.  Its  inva- 
sive power  is  further  illustrated  by  its  penetration  into  the 
heart's  blood  approximately  in  half  this  proportion  of  au- 
topsies. 

Staphylococci  enter  the  bronchi  in  many  instances  (50 
per  cent),  but  relatively  seldom  (15.1  per  cent)  invade  the 
lung  and  rarely  if  ever  penetrate  into  the  blood. 

The  high  incidence,  namely,  84.1  per  cent,  of  B.  influenzae 
in  the  bronchi  is  particularly  noteworthy;  it  exceeds  that 
of  pneumococci,  the  well-recognized  cause  of  lobar  pneu- 
monia, within  the  lung.  It  is  found  much  less  frequently 
within  consolidated  lung  tissue  and  shows  no  tendency  to 
invade  the  heart's  blood.  B.  influenzae  finds  the  most  fa- 
vorable conditions  for  its  multiplication  within  the  bronchi. 

In  view  of  the  frequent  occurrence  of  coexisting  lobar 
and  bronchopneumonia  it  has  appeared  desirable  to  de- 
termine how  far  the  existence  of  obvious  bronchopneumonia 
modifies  the  bacteriology  of  lobar  pneumonia.  In  Table 
XXXI  the  incidence  of  pneumococci,  hemolytic  streptococci, 
staphylococci  and  B.  influenzae  after  death  with  lobar  pneu- 
monia on  the  one  hand  is  compared  with  their  incidence 
after  combined  lobar  and  bronchopneumonia  on  the  other. 

Pneumococci  are  found  in  the  lung  more  frequently  with 
lobar  than  with  combined  lobar  and  bronchopneumonia. 
The  incidence  of  hemolytic  streptococci  and  of  staphylo- 
cocci in  the  lung  is  on  the  contrary  higher  when  broncho- 
pneumonia is  associated  with  lobar  pneumonia.  It  is  not 
improbable  that  these  microorganisms  have  a  part  in  the 


L58      PNEUMONIAS  AND   [NFECTIONS  OF  RESPIRATOR"!  TRACT 

Table  x.\ xi 
With  Lobab  Pneumonia  Alone 


HEMOLYTIC 

STAPHYLO- 

15. INFLU- 

PNEU1 oc 

■S. 

STREPTOCOCCI 

COCCI 

ENZA 

u 

Be 

-  - 

td 

1  « 

w 

W 

g  w 

fc 

> 

g 

> 

=    g 

E- 

-     r- 

E- 

•-  r- 

& 

O    Eh 

H 

U    Eh 

.   ij 

_•    /. 

M    y. 

-;  so 

BS    M 

^  <« 

as    r. 

^   «J 

65    W 

c  t 

p    o 

K    O 

O    o 

£    O 

O   O 

K    O 

p    o 

w  o 

X    u 

X    ft. 

6.    ft. 

£    ft. 

ft.  ft. 

X  ft. 

ft.    ft. 

:■  ft. 

ft.  ft. 

Bronchus 

30 

20 

66.6 

9 

30 

15 

50 

26 

86.7 

Lung 

3  1 

2D 

85.2 

7 

20.6 

3 

8.8 

18 

52.9 

Blood 

54 

36 

66.7 

7 

13 

With    Combined   Lobar   and    Bronchopneumonia 


w 
P     a: 

°  1 

6  p 
55   u 

PNEUMOCOCCl 

hemolytic 
streptococci 

STAPHYLO- 
COCCI 

B.  INFLU- 
ENZA 

EH 

s  ° 

2  ft. 

as  x 
w  o 

ft,  ^ 

64.3 
63.2 
63.1 

g 

jH 

s  ° 

X  ft. 

1  w 

O    Eh 

fti    55 

H   O 

ft,  ft. 

> 

EH 

p  o 
£    ft. 

1  B 

O    Eh 

as  55 
w  o 

ft.  ft. 

Eh 
O    O 

X.  a. 

1  £ 

C^    Eh 

es  55 
w  o 
ft.  ft. 

I'.i  onchus 
Lung 

Blood 

14 
19 
33 

9 
12 

21 

5 
6 
4 

34.3 
31.6 

12.1 

7 
5 

50 

26.3 

11 

8 

78.6 
42.1 

production  of  associated  bronchopneumonia.  The  fre- 
quency with  which  microorganisms  invade  the  blood  is  al- 
mosl  identical  in  the  two  groups. 

The  relative  frequency  with  which  different  types  of 
pneumococci  produce  lobar  pneumonia  under  the  conditions 
existing  when  Camp  Pike  was  attacked  by  an  epidemic  of 
influenza  is  indicated  by  Table  XXXII  in  which  in- 
stances of  lobar  pneumonia  alone  and  of  combined  lobar 
and  bronchopneumonia  arc  listed  separately. 

Pneumococcus  I  and  II,  which  are  found  approximately 
in  two-thirds  of  instances  of  lobar  pneumonia  occurring  in 
cities,  have  an  insignificant  part  in  the  production  of  these 
lesions.  Pneumococcus  IV  and  atypical  Pneumococcus  IT, 
which  are  commonly  found  in  the  month,  are  the  predom- 
inant cause  of  these  lesions,  and  with  Pneumococcus  III, 
also  an  inhabitant  of  the  months  of  normal  individuals, 
have  been  the  cause  of  two-thirds  of  all  instances  of  lobar 
pneumonia  observed  in  this  camp. 


PATiioi/xiY  and  bactuuioi/hjy  following  infi.ckxza 


59 


Table  XXXII 
With  Lobar  Pneumonia 


PNEUMO- 

PNEUMO- 

PNEUMO- 

PMEUMO- 

PNEUMO- 

COCCUS 

COOCUS 

coccus 

coccus 

coccus 

M 

*  a 

I 

II 

II  (Atyp.) 

III 

IV 

2  ° 

£  ft, 

H    O 
ft,    ft, 

| 

Eh 
i— i 

2  ° 

!z   ft, 

VA    g 

°  £ 

H    O 

0-     ft. 

> 

O      c 
X      ft. 

»    g 
«    EH 

«    W 

w  o 
ft-   ft. 

E 

p    o 
X   ft. 

E-i 

y,  g 

°  e 

w  o 
ft.  ft. 

g 

X   ^ 
O    o 
'A   ft. 

W    O 
ft,    ft. 

Bron- 

chus 

30 

1 

3.3 

1 

3.3 

4 

13.3 

4 

13.3 

10 

33.3 

Lung 

34 

1 

2.9 

2 

5.9 

9 

26.5 

6 

17.6 

1] 

32.4 

Blood 

54 

2 

3.7 

2 

3.7 

12 

22.2 

3 

5.6 

17 

31.5 

With  Combined  Lobar  and    Bronchopneumonia 


pneumo- 

PNEUMO- 

PNEUMO- 

PNEUMO- 

PNEUMO- 

coccus 

COCCUS 

COCCUS 

COCCUS 

COCCUS 

w 

I 

II 

,  II  (Atyp.) 

III 

IV 

H 

Eh 

EH 

EH 

Eh 

fc  w 

Z    W 

w 

£  w 

H 

fc  g 

eq 

fc    g 

g 

A    g 

o  # 

P 

p  s 

> 

M 

> 

EH 

g 

h- 1 

Eh 

> 

Eh 

°  B 

>— 1 

Eh 
n   2 

w  5; 

£  p 

O    o 

w  o 

p  6 

W    O 

p  o 

w  o 

2    ° 

a  o 

p  o 

H    O 

Q 

2  a, 

a.  ft. 

%■  ft. 

ft,    ft. 

Jz;  ft. 

ft.  ft. 

£    ft. 

ft.  ft. 

Bron- 

chus 

14 

2 

14.3 

1 

7.1 

3 

21.4 

3 

21.4 

Lung 

19 

1 

5.3 

5 

26.3 

6 

31.6 

Blood 

33 

2 

6.1 

3 

9.1 

4 

12.1 

12 

36.4 

There  is  no  noteworthy  difference  in  the  occurrence  of 
these  types  of  pneumococci  among  instances  of  lobar  pneu- 
monia, on  the  one  hand,  and  of  combined  lobar  and  broncho- 
pneumonia, on  the  other.  Different  types  exhibit  no  note- 
worthy differences  in  their  ability  to  penetrate  into  lungs 
and  blood. 

Hemolytic  Streptococcus  with  Lobar  Pneumonia. — There 
can  be  no  doubt  that  the  concurrent  infection  with 
microorganisms  other  than  pneumococcus  modifies  the 
progress  of  lobar  pneumonia.  With  lobar  pneumonia  alone 
hemolytic  streptococci  have  entered  the  bronchi  in  30  per 
cent  of  instances  and  have  penetrated  into  the  lungs  in  20.6 
per  cent ;  with  associated  lobar  and  bronchopneumonia  the 
same  microorganism  has  entered  the  bronchi  in  34.3  per 
cent  of  instances  and  invaded  the  lung  in  31.6  per  cent. 
Hemolytic  streptococci  are  the  only  microorganisms  other 
than  pneumococci  which,  in  association  with  lobar  pneu- 


L60      PNEUMONIAS  A.ND   INFECTIONS  OF   RESPIRATORS  TRACT 


monia,  have  found  their  way  from  the  hums  to  the  Mood 
stream;  more  than  one-third  of  all  instances  of  lobar  pneu- 
monia in  which  hemolytic  streptococci  find  entrance  into 
the  bronchi  die  with  streptococcus  septicemia. 

Separation  of  instances  of  lobar  pneumonia  into  groups 
on  the  hasis  of  the  occurrence  of  red  or  gray  hepatization 
shows  that  infection  with  hemolytic  streptococcus  is  more 
likely  to  occur  during  the  early  stages  of  the  disease.  The 
average  duration  of  lobar  pneumonia  with  red  hepatization 
lias  been  .'!."  days,  with  red  and  gray  hepatization,  5J  days, 
and  with  gray  hepatization,  7.5  days.  Infection  with  hemo- 
lytic streptococcus  has  occurred  in  association  with  red  or 
gray  hepatization  as  shown  in  Table  XXXIII. 

Table   XXXIII 


NO.    OF 

XO.    "WITH     HEMO- 

PER   CENT    WITH 

AUTOP- 

LYTIC     STREPTO- 

HEMOLYTIC 

SIES 

COCCUS 

STREPTOCOCCUS 

Lobar  pneumonia  with  red 

hepatization 

lfi 

6 

37.5 

Lobar  pneumonia  with   red  ami 

grav  hepatization 

28 

6 

21.4 

Lobar  pneumonia  with  gray 

hepatization 

20 

1 

5.0 

Notwithstanding  the  longer  duration  of  the  disease  and 
consequent  prolongation  of  exposure  to  infection,  lobar 
pneumonia,  which  has  reached  the  stage  of  gray  hepatiza- 
tion, lias  shown  the  smallest  incidence  of  infection  with 
hemolytic  streptococci.  In  the  stage  of  gray  hepatization 
there  is  diminished  susceptibility  to  secondary  infection 
with  this  microorganism. 

Characterstic  histologic  changes  have  been  found  in  the 
lungs  of  those  who  have  died  with  lobar  pneumonia  fol- 
lowed by  invasion  of  lungs  and  blood  by  hemolytic  strepto- 
cocci {e.g.,  Autopsies  -7'.],  430),  hut  with  no  evidence  of 
suppuration  found  at  autopsy.  Within  the  pneumonic 
lung  occur  patches  of  necrosis  implicating  both  exuded 
cells  and  alveolar  walls;  in  some  places  nuclei  have 
disappeared;  elsewhere  nuclear    fragments  are  abundant. 


PATHOLOGY  AND  BACTKUIOLOO V    FOLLOWING    INFLUENZA      L61 

In  these  patches  of  necrosis  Gram-positive  streptococci  in 
short  chains  occur  in  immense  number.  In  some  instances 
{e.g.,  Autopsies  273,  346,  470)  interlobular  septa  are  very 
edematous  and  often  contain  a  network  of  fibrin;  lymphat- 
ics are  dilated  and  contain  polynuclear  leucocytes  in  abun- 
dance. Streptococci  are  found  within  these  lymphatics. 
The  histologic  changes  which  have  been  described  repre- 
sent the  earliest  stages  of  abscess  formation  and  interstitial 
suppuration,  lesions  almost  invariably  caused  by  hemolytic 
streptococci. 

Relation  of  Lobar  Pneumonia  to  Influenza. — Some  writ- 
ers have  suggested  that  lobar  pneumonia,  heretofore  ob- 
served during  the  course  of  epidemics  of  influenza,  is  an 


>5r-pt.  S 


ZS  30  Oct  5  /O  15  ZO  ZS  30 


Chart  2. — Showing  the  relation  of  (a)  date  of  onset  of  cases  in  which  autopsy  dem- 
onstrated lobar  pneumonia,  indicated  by  upper  continuous  line  with  single  hatch,  and  of 
(i>)  date  of  death  of  these  cases,  indicated  by  lower  continuous  line  with  double  hatch  to 
(c)  the  occurrence  of  influenza,  indicated  by  the  broken  line,  and  to  (d)  the  total  num- 
ber of  fatal  cases  of  pneumonia,  indicated  by  the  broken  dotted  line.  Each  case  of  fatal 
pneumonia  is  indicated  by  one  division  of  the  scale  as  numbered  on  the  left  of  the  chart; 
cases  of  influenza  are  indicated  by  the  numbers  on  the   right  of  the  chart. 


162      PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATORY  TRACT 

Lndependenl  disease  with  no  relation  to  influenza,  both  dis- 
eases being  referable  perhaps  to  similar  meterologic  or 
other  conditions.  Chart  2,  which  shows  by  weeks  from 
September  1  to  October  31  the  relation  of  deaths  I' rem  lobar 
pneumonia  (indicated  by  double  hatch)  to  deaths  from  all 
forms  of  pneumonia,  disproves  this  suggestion.  The  two 
curves  follow  parallel  courses;  thai  representing  lobar 
pneumonia  reaches  a  maximum  approximately  one  week 
after  the  outbreak  of  influenza  had  reached  its  height.  Lo- 
bar pneumonia,  like  other  ''onus  of  pneumonia,  was  second- 
ary to  influenza.  When  a  chart  is  plotted  to  represent  the 
dales  of  onset  of  fatal  eases  of  lobar  pneumonia  (indicated 
by  single  hatch  in  Chart  2),  it  becomes  evident  that  the 
greatest  number  of  these  cases  of  pneumonia  had  their  on- 
set at  the  beginning  of  the  influenza  epidemic,  approxi- 
mately one  week  before  it  reached  its  height.  Fatal  lobar 
pneumonia  developed  less  frequently  in  the  latter  pari  of 
the  epidemic;  to  obtain  an  explanation  of  this  relation  it  is 
necessary  to  chart  separately  cases  of  lobar  pneumonia  with 
secondary  streptococcus  infection,  for  we  have  already 
learned  that  streptococcus  infection  was  the  predominant 
cause  of  death  in  the  early  period  of  the  influenza  epidemic. 
Exclusion  of  these  instances  of  secondary  streptococcus  in- 
fection makes  no  noteworthy  change  in  the  character  of  the 
chart.  Fatal  lobar  pneumonia,  like  all  forms  of  fatal 
pneumonia  (p.  140),  was  more  frequent  in  the  first  half 
than  in  the  second  half  of  the  epidemic.  This  differ- 
ence is  referable  either  to  greater  virulence  of  the  virus  of 
influenza  or  to  the  greater  susceptibility  of  those  first  se- 
lected by  the  disease  or,  as  more  probable,  to  conditions 
such  as  crowding  together  of  patients  with  influenza,  favor- 
ing the  transmission  of  microorganisms  which  cause  pneu- 
monia. 

Bronchopneumonia 
For  the  purpose  of  the  present  study  it  is  convenient  to 
•jroii))  together  instances  of  bronchopneumonia  which  have 


PATHOLOGY  AND  BAOTttTMOT.OGY   FOLLOWING    INFLUENZA     L63 

been  unaccompanied,  on  the  one  hand,  by  lobar  pneumonia 
(]).  155)  or,  on  the  other  hand,  by  suppuration,  which  with 
few  exceptions  is  caused  ])y  hemolytic  streptococci  or  by 
staphylococci.  A  group  of  cases  in  which  lobar  and  bron- 
chopneumonia have  occurred  in  the  same  individual  have 
already  been  considered.  In  many  instances,  bronchopneu- 
monia is  accompanied  by  abscess  formation  or  by  some 
other  form  of  suppuration;  these  lesions  will  be  discussed 
elsewhere. 

Bronchopneumonia  unaccompanied  by  lobar  pneumonia 
or  by  suppuration  occurred  in  80  autopsies. 

Pneumonic  consolidation  distributed  with  relation  to  the 
bronchi  exhibits  considerable  variety,  and  an  attempt  to 
define  a  type  of  bronchopneumonia  characteristic  of  influ- 
enza would  be  futile.  Nevertheless,  the  bronchopneumonia 
of  influenza  has  in  many  instances  distinctive*  characters. 

Lesions  of  bronchopneumonia  which  are  frequently 
found  in  the  autopsies  under  consideration  may  be  con- 
veniently designated  by  descriptive  terms,  indicative  of 
their  location  in  the  lung  tissue.  These  lesions,  of  which 
two  or  more  often  occur  in  the  same  lung,  are : 

1.  Peribronchiolar  consolidation  with  which  the  inflam- 
matory exudate  is  limited  to  the  alveoli  in  the  immediate 
neighborhood  of  the  bronchioles. 

2.  Hemorrhagic  peribronchiolar  consolidation  in  which 
gray  patches  of  peribronchiolar  pneumonia  occur  upon  a 
deep  red  background  produced  by  hemorrhage  into  alveoli. 
Pfeiffer  believed  that  this  lesion  was  characteristic  of  in- 
fluenza. 

3.  Lobular  consolidation  with  which  consolidation  is  lim- 
ited to  lobules  or  groups  of  lobules. 

4.  Peribronchial  pneumonia  with  which  small  bronchi  are 
encircled  by  pneumonic  consolidation. 

Each  one  of  these  lesions  will  be  discussed  separately. 
Following  is  a  list  of  the  bacteria  which  have  been  iso- 
lated from  the  consolidated  lung  of  individuals  with  bron- 


L64      PNEUMONIAS  AND   INFECTIONS  OF   RESPIRATOR'S  TRACT 

chopneumonia  unaccompanied  by  Lobar  pneumonia  or  by 
suppuration : 

B.  influenzse  1 

Pneumococci     5 

s.    hemolyl  icus    5 

S.  viridans   1 

B.   influenzse,  pneumococci    si 

B.  influenzse,  S.  hemolyticus  4 

B.  influenzae,  staphylococci  4 

Pneumococci,  S.  hemolyticus   1 

I'liriiiiKHM.rri,    staphylococci     2 

S.  hemolyticus,  staphylococci    1 

S.  hemolyticus,  B.  coli   1 

Staphylococci,   S.   viridans    I 

Stapliylococci.   B.   coli    1 

B.   influenzse,   pneumococci,  stapliylococci    1 

B.  influenzse,  pneumococci,  S.  viridans   1 

B.   influenzse,  S.  hemolyticus,  staphylococci   - 

B.  influenzse,  pneumococci,  staphylococci,  S.  viridans  1 

No  microorganisms  found    6 

47 

The  similarity  of  this  list  to  that  representing  the  bac- 
teriology of  bronchitis  is  evident;  there  is  the  same  multi- 
plicity of  microorganisms  and  the  frequent  occurrence  of 
mixed  infections.  B.  influenzae  is  much  less  frequently 
found  in  the  lung.  The  relative  pathogenicity  of  the  large 
group  of  microorganisms  enumerated  above  is  better  indi- 
cated by  the  following  list  which  shows  what  microorgan- 
isms have  penetrated  into  the  blOod  in  autopsies  performed 
on  individuals  with  bronchopneumonia: 

Pneumococci    20 

S.   hemolyticus    23 

S.    viridans    .1 

Pneui ;occi,   S.  hemolyticus   2 

No    bacteria    found    2.1 

Total 71 

Table  XXXIV  shows  the  percentage  incidence  of  pneu- 
mococcus,    hemolytic    streptococcus,    staphylococcus    and 


PATHOLOGY  AND  BACTI5IUOLO0Y    FOLLOWING    I  X  KLCKX/A 


1  65 


B.  influenzas  in  the  bronchi,  lungs  and  blood  and  is  in- 
serted for  comparison  with  the  similar  table  (Table  XXX) 
showing  the  incidence  of  these  bacteria  in  lobar  pneumonia. 


Table  XXXIV 


PNEUMO- 

HEMOLYTIC 

STAPHYLO- 

B. INFLU- 

w 

COCCI 

STREPTOCOCCI 

COCCI 

ENZAE 

H 

Eh 

EH 

Eh 

w 

W 

J5    W 

H 

£  w 

w 

£    W 

g 

Y<  r 

> 

Eh 

> 

En 

•    02 

03    3 

> 

Eh 

°  B 

P3    02 

Eh 

S3    02 

6  o 

O    o 

W    O 

O    o 

W    O 

O    o 

H    O 

^  o 

£    Ph 

Ph     Ph 

%    Ph 

Ph    Ph 

!Z     Ph 

22 

Ph     Ph 

'A     Ph 

Bronchus 

37 

19 

48.6 

13 

35.1 

59.5 

28 

75.7 

Lung 

47 

20 

42.6 

14 

29.8 

13 

27.7 

23 

48.9 

Blood 

70 

22 

31.4 

24 

34.3 

Table  XXXIV  shows  that  pneumococci  have  a  less  impor- 
tant part  in  the  production  of  broncho  than  of  lobar  pneu- 
monia; with  lobar  pneumonia  this  microorganism  was  found 
in  the  lungs  in  77.3  per  cent  of  instances  and  in  the  blood,  in 
65.5  per  cent,  whereas  with  bronchopneumonia  it  was  found 
in  the  lungs  in  42.6  per  cent  and  in  the  blood  in  31.4  per  cent. 
Hemolytic  streptococci  (in  lungs  and  blood)  and  staphylo- 
cocci (in  lungs),  on  the  contrary,  were  more  common  with 
bronchopneumonia,  and  doubtless  have  a  part  in  the  pro- 
duction of  the  lesion.  Streptococcus  viridans,  B.  coli  and 
M.  catarrhalis,  which  are  not  infrequently  found  in  the 
bronchi  (p.  151),  occasionally  enter  the  lungs  with  bron- 
chopneumonia but  are  rarely  found  with  lobar  pneumonia. 
B.  influenzas  has  been  found  in  less  than  80  per  cent  of 
instances  in  the  bronchi  and  in  about  half  of  the  lungs, 
maintaining  an  incidence  approximately  the  same  as  that 
with  lobar  pneumonia. 

Table  XXXV  shows  the  types  of  pneumococci  found  in 
association  with  bronchopneumonia  and  is  inserted  for 
comparison  with  the  similar  table  (Table  XXXII)  show- 
ing types  of  pneumococci  with  lobar  pneumonia. 

With  broncho  as  with  lobar  pneumonia  pneumococci  com- 
monly found  in  the  mouth,  namely,  atypical  II,  and  Types 
III  and  IV,  have  a  more  important  part  in  production  of  the 


l(i(!      PNEUMONIAS  AXn   [NFECTIONS  OF  RESPIRATORS  TRACT 


TAB!  r    .WW 


PNEUMO- 

PNEUMO- 

PNETJMO- 

PNEUMO- 

PNEUMO- 

COCCTJS 

COCCTJS 

(  oci  US 

(  ii el  s 

COCCUS 

S. 

H 

X 

fe    - 

O    E-. 

.    - 

s  ° 

I 

II 

fAtyp.)    TT 

III 

IV 

- 
> 
Eh 

O    o 
»    Ph 

-  - 

-  ■- 

^   r. 

-  r 
ft.  ft. 

Eh 

_•    /- 

-     C 

V.  ft. 

w  - 

H    O 
-    (V 

e 

Eh 

Z     04 

-     u 

a  o 

ft.    ft. 

> 

5  o 

.4  a. 

«   - 
-    Eh 

ti    /. 
W   O 

ft.  ft. 

si 

g    H 

W    - 

O    Eh 

«  w 
w  o 
a.  ft. 

Bron- 
chus 

37 

1 

2.7 

3 

8  J 

14        37.8 

Lunij 

-17 

•) 

4.3 

2 

L3 

2 

4..,:! 

2 

4.3 

12        2.~>. 2 

Blood 

70 

1          1.4 

1 

1.4 

5 

7.1 

4 

5.7 

1  1        1  5.9 

lesion  than  the  so-called  fixed  types,  I  and  II.  Atypical 
Pneumococcus  II  lias  been  less  frequently  encountered  with 
broncho  than  with  lobar  pneumonia. 

Peribronchiolar  Consolidation. — In  many  instances  of 
bronchopneumonia,  usually  in  association  with  lobular  or 
confluent  consolidation,  small  firm  nodules  of  consolidation 
are  clustered  about  the  bronchioles  (Fig.  -).  These  nodu- 
lar foci  of  consolidation  are  usually  1..1  to  2  mm.  in  diam- 
eter, being  sometimes  slightly  smaller  or  slightly  larger. 
They  are  usually  gray  and  occasionally  surrounded  by  a 
red  halo;  sometimes  they  are  yellowish  gray.  They  are 
clustered  about  the  smallest  bronchial  tubes  to  form  groups 
which  are  from  0.5  to  1  cm.  across.  A  group  of  nodular 
foei  of  consolidation  occupies  the  central  part  of  a  lobule  of 
lung  tissue.  When  pneumonia  has  been  of  short  duration 
these  foci  are  fairly  soft  and  not  sharply  defined,  and  in 
many  instances  this  form  of  bronchopneumonia  is  first  rec- 
ognized by  microscopic  examination.  When  the  disease  has 
lasted  from  ten  days  to  two  weeks,  the  consolidated  nodules 
are  very  firm  and  sharply  circumscribed,  closely  resem- 
bling tubercles.  When  they  have  assumed  this  character, 
microscopic  examination  shows  that  chronic  changes  indi- 
cated by  new  formation  of  interstitial  tissue  have  occurred. 

The  lesion  may  be  designated  peribronchiolar  consolida- 
tion. It  has  occurred  usually  in  association  with  other  types 
of  pneumonic  lesion  in  (il  instances,  being  recognized  at 
autopsy  in  18  and  by  microscopic  examination  in  4.'!. 


PATHOLOGY  AND  BACTERIOLOGY  FOLLOWING  I  \  I'LI '  KX/A  1  67 


Fig.   2. — Acute  bronchopneumonia  with  nodules  of  peribronchiolar  consolidation  and  puru- 
lent bronchitis.     Autopsy  429. 


168      PNEUMONIAS  A\'l»   INFECTIONS  OF   RESPIRATOR'S   TRACT 

In  association  with  this  lesion  there  are  almost  invari- 
ably severe  lesions  of  the  bronchi.  Purulent  bronchitis  was 
noted  in  47  of  the  61  instances,  in  which  this  nodular  bron- 
chopneumonia was  Pound  at  autopsy.  An  index  of  the  se- 
verity of  the  bronchia]  injury  is  the  frequency  with  which 
bronchiectasis  has  occurred;  dilatation  of  small  bronchi 
was  observed  in  24  instances.  In  10  instances  the  bronchi 
were  encircled  by  conspicuous  zones  of  hemorrhage. 

In  association  with  this  peribronchiolar  lesion  the  lung  is 
often  voluminous  and  fails  to  collapse  on  removal  from  the 
chest.  Pressure  upon  the  lung  squeezes  from  the  smallest 
bronchi,  both  in  the  neighborhood  of  the  nodular  consolida- 
tion and  elsewhere,  a  droplet  of  viscid,  semifluid  mucopuru- 
lent material.  The  presence  of  this  tenacious  material 
throughout  the  small  bronchi  doubtless  explains  the  failure 
of  the  lung  tissue  to  collapse.  Interstitial  emphysema  has 
been  present  in  some  of  these  lungs. 

A  red  zone  of  hemorrhage  has  occasionally  been  observed 
about  the  Foci  of  peribronchiolar  pneumonia.  A  further 
stage  in  the  same  process  is  represented  by  hemorrhage 
into  all  of  the  alveoli  separating  these  patches  of  consolida- 
tion. This  hemorrhagic  lesion,  which  will  be  described  in 
more  detail  later,  has  been  found  repeatedly  in  the  same 
lung  with  peribronchiolar  pneumonia,  being  present  in  8 
among  the  61  autopsies  cited.  Lobular  bronchopneumonia 
accompanied  the  peribronchiolar  lesion  27  times  and  lobar 
pneumonia  accompanied  it  20  times. 

When  an  abscess  caused  by  hemolytic  streptococcus  is 
associated  with  peribronchiolar  pneumonia,  empyema  is 
present,  but  otherwise  pleurisy  is  absent  or  limited  to  a 
scant  fibrinous  exudate. 

Histologic  examination  demonstrates  very  clearly  the  re- 
lation of  this  lesion  to  the  bronchioles  (Fig.  II).  These 
passages  are  tilled  and  distended  with  an  inflammatory  ex- 
udate consisting  almosl  entirely  of  polynuclear  leucocytes. 
The   respiratory  bronchioles  are  beset  with  alveoli  often 


PATHOLOGY  AND  BACTERIOLOGY    FOLLOWING    INFLUENZA      169 

limited  to  one  sido  of  the  tubule  and  these  alveoli  are  filled 
with  leucocytes.  The  alveolar  duets,  distinguishable  from 
the  bronchioles  by  the  absence  of  columnar  or  cubical  epi- 
thelium and  by  possession  of  smooth  muscle,  are  similarly 
filled  with  leucocytes;  the  numerous  alveoli  which  form  the 
walls  of  the  alveolar  ducts  are  distended  by  an  inflamma- 
tory exudate.    In  sections  which  pass  through  an  alveolar 


Fig.  3. — Acute  bronchopneumonia  with  peribronchiolar  consolidation;  a  respiratory 
bronchiole  partially  lined  by  columnar  epithelium  passes  into  alveolar  duct  and  the  adja- 
cent alveoli   are   filled   by   polynuclear   leucocytes.     Autopsy   333. 


duct  and  one  or  more  of  its  infundibula,  the  further  exten- 
sion of  the  lesion  may  be  determined  (Fig.  4).  The  infun- 
dibulum  in  proximity  with  the  alveolar  duct  contains  poly- 
nuclear leucocytes  and  the  same  cells  are  seen  in  the  alveoli 
which  here  form  its  wall,  but  the  intensity  of  the  inflamma- 
tory reaction  diminishes  toward  the  periphery,  so  that  the 
distal  part  of  the  infundibulum,  which  is  much  distended 


L70      PNEUMONIAS  A.ND   [NFECTIONS  OF   RESPIRATORS   TRACT 


and  in  consequence  mere   readily  definable  than   usual,  is 
free  from  inflammatory  exudate. 

Occasionally  there  is  irregularly  distributed  hemorrhage 
and  perhaps  some  edema  in  the  alveoli  immediately  adja- 
cent to  those  which  form  the  peribronchiolar  focus  of  in- 
flammation. In  such  instances  small  bronchi,  thai  is,  air 
passages,  lined  by  columnar  epithelium  and  devoid  of  trib- 


utary alveoli,  may  be  surrounded  by  a  /one  of  hemorrhage; 
immediately  surrounding  the  bronchus,  the  wall  of  which 
shows  intense  inflammation,  alveoli,  in  a  /one  of  which  the 
radius  represents  several  alveoli,  are  filled  with  blood.  This 
hemorrhagic  /one  is  continued  Prom  the  bronchus  over  the 
focus  of  inflammation  which  surrounds  the  bronchiole, 


PATHOLOGY  AND  BACTEUIOLO( J V    FOLLOWING    INFLUENZA      171 

Another  variation  in  the  character  of  the  lesion  is  doubt- 
less referable  to  variation  in  the  severity  of  primary  bron- 
chial injury.  Alveoli  immediately  surrounding  small  bron- 
chi are  filled  with  dense  plugs  of  fibrin.  The  alveoli  which 
beset  the  walls  of  the  bronchioles  contain  fibrin,  bu1  the 
alveolar  duct  and  its  tributary  alveoli  are  filled  with  poly- 
nuclear  leucocytes. 

The  bacteria  which  have  been  cultivated  from  the  lung  in 
autopsies  with  peribronchiolar  pneumonia  are  as  follows : 

Fneumococcus    5 

S.   hemolyticus    8 

B.    influenzae,   pneumococcus    5 

B    influenzas,  S.  hemolyticus   7 

B.  influenzas,   staphylococcus    1 

Fneumococcus,    staphylococcus    2 

S.  hemolyticus,   staphylococcus    2 

B.  influenzae,  pneumococcus,   S.  hemolyticus    2 

B.  influenzae,  pneumococcus,  staphylococcus   1 

B.  influenzae,  S.  hemolyticus,  staphylococcus 2 

Pneumococcus,   S.   hemolyticus,   staphylococcus 3 

No   organism    3 

Total   41 

The  following  list  which  shows  the  bacteria  found  in  the 
blood  is  an  index  to  the  pathogenicity  of  pneumococci  and 
hemolytic  streptococci : 

Pneumococcus    .  . 22 

S.  hemolyticus 20 

Pneumococcus,    S.   hemolyticus    1 

No  organism    11 

Total   57 

The  percentage  incidence  of  pneumococcus,  hemolytic 
streptococcus,  staphylococcus  and  B.  influenzae  in  bronchus, 
lung  and  blood,  given  in  Table  XXXVI,  is  inserted  to 
indicate  with  what  readiness  each  one  of  these  microorgan- 
isms passes  from  the  bronchus  through  the  lung  into  the 
circulating  blood. 


L72      PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATORY   TRACT 

Table  XXXVI 


HEMOLYTIC 
PNEUMOCOCCUS 

STREPTOCOCCUS 

STAPHS  l.ii- 
COCCUS 

li.  INFLUENZA 

Bronchus 

Lung 

Blood 

•     39.4'  i                       .17.7% 
4.:.'.",                    r.i.o% 
40.3%                        36.8% 

60.67o 
21.9% 

0.  % 

84.8% 
43.9% 

0.  % 

B.  influenzae  is  presenl  in  the  bronchi  in  a  very  Large  pro- 
portion (84.8  per  cent )  of  those  in  whom  this  type  of  bron- 
chopneumonia has  been  round  at  autopsy;  it  is  much  less 
frequently  recovered  from  the  Lungs.  Staphylococci,  in 
pari  S.  albus  and  in  part  S.  aureus,  are  less  frequently 
found  in  the  bronchi  and  are  recovered  from  the  Lungs  in  a 
relatively  small  proportion  of  autopsies.  The  percentage 
incidence  of  piieiunococci  and  streptococci  in  Lungs  and 
blood  demonstrates  the  pathogenicity  of  these  microorgan- 
isms, for  whereas  pneumococci  and  hemolytic  streptococci 
are  found  iii  the  consolidated  lungs  in  43.9  and  61.0  per 
cent  o!'  instances  of  the  lesion  respectively,  they  make  their 
way  into  the  blood  in  40.3  and  36.8  per  cent  of  instances. 

Coexisting-  infection  with  pneumococci  and  hemolytic 
streptococci  has  been  not  uncommon  e.g.,  Autopsy  275  in 
which  both  were  in  the  blood;  in  2  instances  (Autopsies  333 
and  378)  in  which  pneumococci  were  obtained  from  the 
blood,  hemolytic  streptococci  were  found  in  the  lungs  and 
bronchi;  in  3  instances  (Autopsies  258,  27.".  and  445)  in 
which  hemolytic  streptococci  were  present  in  the  blood, 
pneumococci  were  obtained  from  the  lungs. 

In  the  group  of  autopsies  under  consideration,  examina- 
tion of  the  sputum  was  made  during  life  and  after  onset  of 
pneumonia  in  11  instances.  The  microorganisms  found  in 
the  sputum  and  at  autopsy  were  as  follows : 

IN    BLOOD,    U'XCX    OK    BRONCHUS 
SPUTUM  AT     AUTOPSY 

Autopsy     240        Pneum.  IV  Pneum.  IV 

246  Pneum.  atyp.  TT,  B.  inf. 

247  Pneum.  IV,  B.  inf.  Pneum.  IV 

250  Pneum.  atyp.  II,  B.  inf.  Pneum.  atyp.   II 

253  Pneum.  atyp.   II  Pneum.     II 

285  Pneum.  atyp.  II,  B.  Inf.  ft.  hem.,  B.   inf. 

288  S.  hem.,  B.  inf.  ft.   hem.,  B.   inf. 


PATHOLOGY  AND  BACTERIOLOGY    FOLLOWING   INFLUENZA     173 

]X     BLOOD,     LUNGS     QB    BRONCHUS 
SPUTUM  AT  AUTO) 

Autopsy    291  Pneum.  IV,  B.  inf.  Staph.,  E.  inf. 

300         Pneum.  atvp.  II,  B.  inf.  Pneum.  atyp.  IT,  P..  inf. 

312  Pneum.  IV,  S.  hem.,  B.  inf.        S.   hem.,    P..   inf. 

:;4<;         Pneum.  IV,  B.  inf.  S.   hem,   B.  inf. 

Iii  2  instances  (Autopsies  285  and  346)  among  this  small 
group  of  eases,  pneumoeocci  but  no  hemolytic  streptococci 

were  found  in  the  sputum  several  days  before  death., 
whereas  death  occurred  as  the  result  of  secondary  invasion 
with  hemolytic  streptococci  and  no  pneumoeocci  were  found 
at  autopsy.  It  is  probable  that  this  sequence  of  event-  - 
not  uncommon.  B.  influenza?  finds  its  way  into  the  bronchi 
and  pneumoeocci  follow  it :  pneumonia  limited  to  peribron- 
chiolar alveoli  may  occur  in  consequence  of  this  invasion. 
Later  hemolytic  streptococci  may  follow  the  same  path  and 
cause  death  with  bacteremia. 

Hemorrhagic  Peribronchiolar  Consolidation. — Peribron- 
chiolar pneumonia  accompanied  by  diffuse  accumulation 
of  blood  within  the  alveoli  is  one  of  the  most  frequent  com- 
plications of  influenza.  The  lung  tissue  is  laxly  consoli- 
dated, and  on  section  there  is  a  homogeneous  dull  deep  red 
background  upon  which  are  seen  small  gray  spots  (1.5  to  2 
mm.  in  diameter)  grouped  in  clusters  about  the  smallest 
bronchi  (Fig.  5).  Wide  areas  of  lung  tissue  are  implicated 
and  the  lesion  is  more  common  in  the  dependent  parts  of 
the  lung  than  elsewhere.  In  common  with  other  forms  of 
bronchopneumonia  the  lesion  is  in  most  instances  associ- 
ated with  changes  in  the  bronchi :  in  55  instances  of  hemor- 
rhagic bronchiolar  pneumonia  purulent  bronchitis  was 
found  in  43  instances :  it  is  noteworthy  that  purulent  bron- 
chitis often  is  not  evident  in  the  presence  of  pulmonary 
edema  and  edema  is  not  infrequent  with  this  pneumonic 
lesion. 

Microscopic  examination  demonstrates  the  presence  of 
acute  bronchitis:  the  lumina  of  the  small  bronchi  contain 
polynuclear  leucocytes  and  red  blood  corpuscles.  Accumu- 
lation of  blood  may  separate  the  epithelium  from  the  base- 


174      PNEUMONIAS  AND   INFECTIONS  OF   RESPIRATOR!    TRACT 

incut  membrane.  The  mucosa  immediately  below  the  epi- 
thelium contains  polynuclear  leucocytes  in  Pair  abundance 
and  the  blood  vessels  of  the  bronchial  wall  are  much  en- 
gorged. Respiratory  bronchioles  are  distended  with  poly- 
nuclear leucocytes  and  red  blood  corpuscles.  In  a  /one 
aboul  each  bronchiole,  in  areas  corresponding  to  the  small 
gray  spots  seen  upon  the  cut  surface  of  the  hum',  the  alveoli 
are  tilled  with  polynuclear  leucocytes.  In  the  lung  tissue 
intervening  between  these  spots  of  leucocytic  pneumonia 
the  alveoli  are  distended  with  red  blood  corpuscles. 


Fig.  5.— Bronchopneumonia  with  hemorrhagic  peribronchiolar  consolidation. 


In  favorable  sections  it  is  occasionally  possible  to  follow 
the  bronchiole  and  alveolar  duet,  both  tilled  with  leuco- 
cytes, into  an  infundibulum.  The  proximal  part  of  the  in- 
fundibulum  contains  polynuclear  leucocytes,  whereas  the 
distal  part  and  its  tributary  alveoli  are  filled  with  serum 
and  red  blood  corpuscles. 

When  the  lesion  has  persisted  for  a  short  time  there  is 
evidence  of  beginning  migration  of  polynuclear  leucocytes 
from  the  blood  vessels  into  the  alveoli  which  are  filled  with 


Pathology  and  bacteriology  following  ixi'm-kx/a    L75 

Mood.  The  alveolar  walls  contain  numerous  polynuclear 
leucocytes  and  leucocytes  which  have  entered  the  intraal- 
veolar  blood  arc  numerous  in  contael  with  the  wall  bul  occur 
in  scant  number  in  Hie  center  of  the  alveolar  lumen. 

Alveolar  epithelium  in  contact  with  the  blood  in  the  lu- 
men is  usually  swollen  and  often  uniformly  nucleated. 

The  inflammatory  process  is  evidently  transmitted  Prom 
the  bronchioles  and  to  a  less  degree  from  the  small  bronchi 
to  the  adjacent  alveoli.  Polynuclear  leucocytes  fill  the  lu- 
men of  the  bronchiole  and  the  alveoli  immediately  adja- 
cent; at  the  periphery  of  the  focus  of  pneumonia,  the  alve- 
oli may  contain  fibrin.  In  such  instances  small  bronchi 
(lined  by  a  continuous  layer  of  columnar  epithelial  cells) 
may  be  surrounded  by  alveoli  containing  fibrin. 

In  sections  from  one  part  of  the  lung,  the  alveoli  between 
the  peribronchiolar  foci  of  pneumonia  may  be  uniformly 
filled  with  red  blood  corpuscles,  whereas  in  sections  from 
another  part  pneumonic  foci  may  be  surrounded  by  a  zone 
of  intraalveolar  hemorrhage  or  of  hemorrhage  and  edema 
outside  of  which  some  air-containing  tissue  occurs.  There 
are  transitions  between  this  halo  of  intraalveolar  hemor- 
rhage and  edema  surrounding  each  bronchiolar  focus  and 
complete  hemorrhagic  infiltration  of  all  intervening  alveoli. 

Large  mononuclear  cells  are  occasionally  fairly  numer- 
ous within  the  alveoli  containing  blood.  These  cells  act  as 
phagocytes  ingesting  red  corpuscles,  so  that  at  times  they 
are  filled  with  corpuscles.  Disintegration  of  red  corpuscles 
occurs  and  brown  pigment  remains  within  the  cell.  It  is 
not  uncommon  to  find  numerous  mononuclear  pigment  con- 
taining cells  which  resemble  those  found  with  chronic  pas- 
sive congestion  of  the  lungs. 

Lungs,  the  site  of  hemorrhagic  peribronchiolar  pneumo- 
nia, may  undergo  chronic  changes  which  will  be  described 
elsewhere. 

The  lesion  which  has  been  designated  hemorrhagic  peri- 
bronchiolar pneumonia  is  that  which  Pfeiffer  regarded  as 


176      PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATOR'S  TRACT 

the  characteristic  type  of  influenzal  pneumonia.  In  the 
small  bronchi  containing  pus  and  in  lung  tissue,  Pfeiffer 
-laics,  influenza  bacilli  arc  predominant  and  present  in  as- 
tonishing riumber  in  smear  preparations.  The  demonstra- 
tion of  I).  influenzae  by  cultures  from  pneumonic  lung  is 
mentioned  by  him  bul  its  association  with  oilier  microor- 
ganisms in  such  cultures  is  not  discussed. 

Microorganisms  which  we  have  isolated  from  the  Lungs 
of  individuals  with  hemorrhagic  peribronchiolar  pneumo- 
nia are  as  follows : 

B.    influenzae    1 

Pneumoeoccus    2 

s.  hemolyticus   10 

B.   influenzae,  pneumococcus   7 

15.  influenzae,  S.  hemolyticus  3 

B.  influenza',  staphylococcus  2 

S.  hemolyticus,  B.  coli   3 

B.  influenza1,  pneumococcus,  staphylococcus   2 

B.  influenza',  S.  hemolyticus,  staphylococcus 5 

Pneumococcus,  S.  hemolyticus,  staphylococcus  1 

No  organisms  2 

Total    38 

With  this  type  of  pneumonia  B.  influenzae  has  not  been 
isolated  in  pure  culture:  B.  influenzae  alone  is  recorded  only 
once  (Autopsy  435),  but  in  this  instance  the  culture  has 
been  so  obscured  by  contamination  that  the  occurrence  of 
pneumococci  or  streptococci  cannot  be  excluded;  S.  hemo- 
lyticus lias  doubtless  been  present  in  this  lung,  Tor  it  has 
been  found  in  the  heart's  blood,  in  the  bronchus,  and  in  the 
peritoneal  exudate  of  the  same  individual. 

The  incidence  of  pneumococci  and  hemolytic  streptococci 
in  this  list  does  not  differ  materially  from  that  with  peri- 
bronchiolar pneumonia  unaccompanied  by  extensive  intra- 
alveolar  hemorrhage,  though  hemolytic  streptococci  are 
somewhat  more  frequent  with  the  hemorrhagic  lesion.  The 
following  table  shows  the  frequency  with  which  pneumo- 
cocci and  hemolytic  streptococci  have  penetrated  into  the 
blood : 


PATHOLOGY  AND  BACTERIOLOGY    FOLLOWING   INKLUEXZA     177 

Pncumococcus    11 

S.   hemolyticus    24 

Pneumococcus,    S.   hemolyticus    1 

No  organism   J  2 

Total   48 

Table  XXXVII  showing  the  percentage  incidence  of 
pneumococci,  hemolytic  streptococci,  staphylococci  and  I>. 
influenzas  further  emphasizes  the  similarity  between  the 
bacteriology  of  peribronchiolar  pneumonia  (Table  XXXVI) 
and  the  closely  related  hemorrhagic  lesion : 

Table  XXXVII 


Bronchus 
Lung 
Blood 
of  heart 


PXEUMOCOCCUS 


44.0% 
31.6% 
25.0% 


HEMOLYTIC 
STREPTOCOCCUS 


64.0% 
57.9% 
52.1% 


STAPHYLO- 
COCCUS 


44.0% 

26.8% 
0% 


B.   INFLUENZAE 


72.0% 

52.6% 

0% 


Pneumococci  have  been  found  in  the  lungs  (31.6  per 
cent)  and  blood  (25  per  cent),  somewhat  less  frequently 
than  with  peribronchiolar  pneumonia  (43.9  and  40.3  per 
cent  respectively),  and  hemolytic  streptococci  have  been 
found  in  the  blood  more  frequently  (52.1  per  cent)  than 
with  the  latter  (36.8  per  cent)  but  otherwise  the  bacteriol- 
ogy of  the  two  lesions  corresponds  closely.  The  low  inci- 
dence of  B.  influenzas  in  the  bronchi  (72  per  cent)  with  hem- 
orrhagic peribronchiolar  pneumonia  is  perhaps  incorrect 
as  the  result  of  the  relatively  small  number  of  bacteriologic 
examinations  (namely,  25),  but  the  incidence  of  the  same 
microorganism  in  the  lung  has  been  higher  (52.6  per  cent) 
than  with  nonhemorrhagic  peribronchiolar  lesion  (43.9  per 
cent). 

In  some  instances  infection  with  hemolytic  streptococci 
has  occurred  after  the  onset  of  pneumonia.  The  following 
list  compares  the  results  of  bacteriologic  examination  of 
the  sputum  made  after  the  onset  of  pneumonia  with  that  of 
blood,  lungs  or  bronchus  after  death : 


178      PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATORY   TRACT 


SIM  TIM 

IX    BLOOD,    LUNGS    OK    BRONCHUS 
AT   AUTOPSY 

Aut< 

ipsy  237 

s.  hem. 

s.  hem. 

242 

Pneum.  atyp.    II,   B. 

inf. 

Pneum.  atyp.   1 1 

2  17 

Pneum.    IV,   B.  inf. 

Pneum.   1  V 

266 

s.  hem. 

S.  hem.,  n.  inf. 

346 

Pneum.  IV.  B.  inf. 

S.  hem.,  B.  inf. 

376 

|  No.  s.  hem.) 

s.  hem.,  staph.,  1'..  inf. 

Instances  of  secondary  infection  with  hemolytic  strepto- 
coccus occur  in  the  list,  namely,  Autopsies  346  and  376. 

From  the  foregoing  studies  of  the  bacteriology  of  peri- 
bronchiolar and  hemorrhagic  peribronchiolar  pneumonia 
the  following  conclusions  may  be  drawn:  (a)  B.  influenzae 
is  found  in  most  instances  of  these  lesions  in  the  bronchi 
and  in  aboul  half  of  all  instances  in  the  lungs,  but  does  not 
occur  unaccompanied  by  other  microorganisms,  (h)  In  a 
considerable  number  el'  autopsies  pneumococcus  is  the  only 
microorganism  that  accompanies  B.  influenzae;  from  the 
lungs  it  penetrates  into  the  blood  from  which  it  is  obtained 
in  pure  culture,  (c)  In  a  considerable  number  of  instances 
8.  hemolyticus  accompanies  B.  influenzae,  and  in  some  of 
these  instances  (representing  a  large  proportion  of  the  rel- 
atively small  number  of  eases  examined  during  life),  exam- 
ination of  the  sputum  has  demonstrated  that  infection  has 
been  secondary  to  a  pneumonia  with  which  no  hemolytic 
streptococci  have  been  found  in  the  sputum. 

Lobular  Consolidation. — Consolidation  of  scattered  lob- 
ules or  groups  of  lobules  has  occurred  in  nearly  all  in- 
stances, namely,  71  of  80  autopsies  with  bronchopneumonia 
unaccompanied  by  lobar  pneumonia  or  by  suppuration. 
When  death  follows  shortly  after  the  onset  of  pneumonia, 
patches  of  consolidation  have  a  dull  deep  red  color;  blood- 
tinged  fluid  escapes  from  the  cut  surface  which  is  almost 
homogeneous  or  finely  granular.  The  consolidated  tissue 
seen  through  the  pleura,  which  is  raised  above  the  general 
level,  has  a  bluish  red  color.  Isolated  lobules  or  groups  of 
lobules  which  have  undergone  consolidation  may  be  scat- 
tered throughout  the  lungs,  but  nol  infrequently  there  is 
confluent    consolidation    of    the    greater   part    of   lobes,    of 


PATHOLOGY  AND  BACTERIOLOGY   FOLLOWING    IX  FLCKX/A     170 

whole  lobes  or  of  almost  an  entire  Lung.  Such  Lungs  are 
very  heavy  and  may  weigh  1,400  or  1,500  grains;  bloody 
serous  fluid  exudes  from  the  cut  surface.  The  lesion  resem- 
bles the  red  hepatization  of  lobar  pneumonia,  but  confluent 
patches  of  pneumonia  are  usually  well  defined  by  lobule 
boundaries.  The  tissue  is  soft  and  the  granulation  of  lobar 
pneumonia  is  absent.  In  many  instances  the  lobular  or  con- 
fluent areas  of  consolidation  are  reddish  gray;  in  some  in- 
stances consolidated  tissue  is  in  places  red  and  elsewhere 
gray,  and  in  a  smaller  group  of  autopsies  there  is  gray 
consolidation  only  (Fig.  6).  Ked  lobular  consolidation  is 
often  seen  in  those  who  have  died  within  the  first  four  days 
following  the  onset  of  pneumonia,  but  is  almost  equally  fre- 
quent after  from  five  to  ten  days ;  the  average  duration  of 
pneumonia  in  these  cases  was  5.5  days.  Combined  red  and 
gray  consolidation  was  more  frequently  found  when  pneu- 
monia had  lasted  more  than  five  days,  the  average  duration 
of  pneumonia  being  7.3  days.  The  greater  number  of  in- 
stances of  gray  consolidation  were  found  after  seven  days 
of  pneumonia,  the  average  duration  of  the  disease  being 
10.0  days.  These  figures  are  cited  to  show  that  lobular, 
like  lobar,  consolidation  passes  gradually  from  a  stage  of 
red  to  gray  hepatization,  but  the  change  occurs  more  slowly 
and  is  often  long  delayed. 

Lobular  pneumonia,  which  occurred  71  times  among  80 
cases  classified  as  bronchopneumonia,  may  be  regarded  as 
an  almost  constant  lesion  of  the  disease.  It  is  found  not 
only  in  association  with  other  lesions  of  bronchopneumo- 
nia, but  with  lobar  pneumonia  of  influenza  as  well. 

The  bacteriology  of  this  lesion  shows  no  deviation  from 
that  of  the  slightly  larger  group  of  bronchopneumonia 
(p.  163).  All  types  of  pneumococcus  have  been  found  in 
association  with  the  lesion,  Pneumococcus  I  in  2  instances, 
Pneumococcus  II  in  1  instance;  atypical  Pneumococcus  II 
and  Pneumococcus  IV  have  been  found  much  more  fre- 
quently.    Pneumococci  have  been  found  in  more  than  a 


ISO      PNEUMONIAS  A.ND   [NFECTIONS  OF  RESPIRATOR'S    CRACT 


Fie  6— Acute  bronchopneumonia  with  confluent  gray  lobular  consolidation  in  lower 
part  of  upper  lobe  and  hemorrhagic  peribronchiolar  pneumonia  in  lower  lobe;  purulent 
bronchitis. 


PATHOLOGY  AND    IJACTKUIOLOOY    FOLLOWING    I  N  VIA  'KXZA      LSI 

third  of  these  autopsies  (42.9  per  cenl  in  the  lungs,  33.3  per 
cent  in  the  blood) ;  hemolytic  streptococci  in  less  than  one- 
third  (28.5  per  cent  in  the  lungs,  30.2  per  cent  in  the  blood). 
The  following  list  shows  the  bacteriology  of  a  small 
group  of  autopsies  in  which  the  sputum  was  examined  after 
onset  of  pneumonia : 

SPUTUM  BLOOD,    LUNGS    OR   BRONCHI'S    AT 

AUTOPSY 

Autopsy  233  Pneum.   atyp.  II  Pneum. 

237  S.  hem.  S.    hem. 

242  Pneum.   atyp.   II,  B.  inf.  Pneum.   atyp.  II 

250  Pneum.   atyp.  II,  B.  inf.  Pneum.    atyp.    II 

253  Pneum.  atyp.  II  Pneum.  atyp.  II,  staph.,  B.  inf. 

266  S.  hem.  S.  hem.,  B.  inf. 

274  Pneum.    IV  S.  hem. 

291  Pneum.    IV,    B.    inf.  Staph.,  B.  inf. 

312  Pneum.  IV,  S   hem.,  B.  inf.         S.  hem.,  staph.,  B.  inf. 

In  one  instance  of  streptococcus  pneumonia  (Autopsy 
274)  infection  with  streptococci  occurred  subsequent  to  the 
examination  of  the  sputum  made  five  days  before  death; 
pneumococcus  was  found  in  the  washed  sputum. 

With  lobar  pneumonia  there  was  evidence  that  superim- 
posed infection  occurred  more  frequently  during  the  stage 
of  red  than  of  gray  hepatization.  With  the  lobular  con- 
solidation of  bronchopneumonia  this  relation  has  not  been 
found.  Among  27  instances  of  red  lobular  consolidation, 
hemolytic  streptococcus  has  occurred  6  times,  namely  in 
22.2  per  cent ;  among  26  instances  of  red  and  gray  consol- 
idation, 8  times,  namely,  in  30.7  per  cent;  among  13  in- 
stances of  gray  consolidation,  5  times,  namely,  in  38.5  per 
cent.  Infection  with  hemolytic  streptococci  is  more  fre- 
quent when  the  lesion  has  persisted  to  the  stage  of  gray 
hepatization.  This  difference  between  lobar  and  broncho- 
pneumonia is  probably  dependent  in  part  at  least  upon  the 
more  severe  and  persistent  lesions  of  the  bronchi  with 
bronchopneumonia. 

The  histology  of  consolidation  which  is  definitely  limited 
to  secondary  lobules  or  groups  of  lobules  varies  consider- 
ably.   When  death  occurs  in  the  early  stage  of  the  lesion, 


L82      PNEUMONIAS  AXI»   [INFECTION'S  OF   RESPIRATOR'S   TRACT 

consolidated  patches  are  deep  red  and  somewhal  edema- 
tous, so  that  bloody  serous  fluid  escapes  from  the  cut  sur- 
face of  the  Lung  and  red  blood  corpuscles  are  present  in  the 
alveoli  in  greal  abundance  together  with  polynuclear  leu- 
cocytes, fibrin  and  serum  in  varying  quantity.  It  is  not 
uncommon  to  find  evidence  thai  the  lesion  lias  had  its  or- 
igin in  the  bronchioles  and  extended  Prom  them  to  other 
parts  of  the  lobule.  Polynuclear  leucocytes  max-  be  rela- 
tively abundant  within  and  immediately  about  the  bronchi- 
oles and  alveolar  ducts,  whereas  the  intervening  alveoli  and 
infundibula  are  filled  with  red  blood  corpuscles  among 
which  are  polynuclear  leucocytes  and  perhaps  some  fibrin. 
It  may  be  evident  that  bronchiolar  pneumonia  with  hemor- 
rhage into  intervening  alveoli  is  in  process  of  transforma- 
tion into  a  more  diffuse  leucocytic  pneumonia.  Tor  polynu- 
clear leucocytes  are  making  their  way  from  the  alveolar 
wall  into  the  blood-filled  lumen  and,  as  the  result  of  the 
presence  of  blood,  remain  for  a  time  close  to  the  lining  of 
the  alveolus. 

When  the  consolidated  lobules  have  assumed  a  gray  or 
reddish  gray  color,  jiolyiruclear  leucocytes  are  more  abun- 
dant and  often  almost  homogeneously  pack  every  alveolus 
within  the  boundaries  of  the  lobule.  In  some  instances 
there  is  fibrin  partially  obscured  by  the  presence  of  leuco- 
cytes in  great  number. 

Although  fibrin  is  less  abundant  with  bronchopneumonia 
than  with  lobar  pneumonia,  nevertheless  in  a  considerable 
proportion  of  instances  it  is  a  very  conspicuous  element 
of  the  inflammatory  exudate  within  the  bronchioles,  alve- 
olar ducts  and  alveoli.  It  is  unusual  to  find  the  alveolar 
ducts  and  alveoli  uniformly  plugged  with  fibrin  containing 
leucocytes;  there  is  a  variegated  distribution  of  exudate 
which  has  little  resemblance  to  that  of  lobar  pneumonia. 
Occasionally  (Autopsies  242  and  247)  polynuclear  leuco- 
cytes (ill  the  bronchioles,  alveolar  ducts  and  infundibula, 
whereas  the  surrounding  tributary  alveoli  contain  fibrin 


PATHOLOGY  A5TD  BACTEIt  10 I, 00  Y    FOLLOW  I  NO    INFLUENZA      L83 

and  polynuclear  leucocytes  in  moderate  number;  red  blood 
corpuscles  may  be  present  iir sufficient  number  to  give  a 
homogeneously  red  color  to  the  lobular  consolidation. 

In  association  with  lobular  pneumonia,  fibrin  within  the 
lung  tissue  undergoes  certain  changes  which  outline  very 
sharply  the  alveolar  ducts  and  the  other  structures  usually 
ill  defined  in  preparations  of  the  lung.  A  remarkable  ap- 
pearance is  produced  by  the  deposit  of  hyalin  fibrin  upon 
the  surface  of  the  alveolar  ducts  and  infundibula.  This 
lesion  has  been  described  by  LeCount. 

Within  the  alveolar  tissue  of  the  lung,  spaces  are  seen 
lined  by  a  layer  of  fibrin  which  stains  homogeneously  and 
very  brightly  with  eosin.  They  are  recognized  as  alveolar 
ducts  b}^  the  presence  of  scattered  bundles  of  smooth 
muscle  in  their  wall.  The  layer  of  hyaline  fibrin  overlying 
the  surface  of  the  alveolar  duct  usually  forms  a  continuous 
lining  and  covers  over  the  orifices  of  the  alveoli  which  sur- 
round the  alveolar  duct,  These  ducts  are  rendered  still 
more  conspicuous  by  the  character  of  their  contents  which 
exhibits  a  sharp  contrast  with  that  of  the  surrounding 
alveoli.  The  alveoli  duct  occasionally  contains  a  bubble  of 
air,  but  more  frequently  it  is  filled  with  serum  in  which  red 
blood  corpuscles  are  sometimes  numerous.  There  is  within 
the  lumen  scant  fibrin  and  very  few  cells,  among  which  poly- 
nuclear leucocytes  are  predominant.  In  the  surrounding 
alveoli  on  the  contrary  leucocytes  and  fibrin  are  abundant. 
A  similar  change  is  found  in  the  infundibula  very  clearly 
defined  by  their  conical  form,  which  is  especially  well  out- 
lined below  the  pleura  or  in  contact  with  interlobular  septa. 
The  infundibulum  is  outlined  by  hyaline  fibrin  which  passes 
over  the  orifices  of  the  tributary  alveoli  and  separates  the 
serous  contents  of  the  infundibulum  from  the  cellular  fibrin- 
ous contents  of  the  alveoli  about. 

The  lesion  which  has  been  described  is  often  associated 
with  acute  bronchitis  and  bronchiolitis,  and  the  alveoli  im- 
mediately about  the  respiratory  bronchioles  may  be  filled 


1S4      PNEUMONIAS  AXI>   [NFECTIONS  OF   RESPIRATOR'S  TRACT 

with  polynuclear  Leucocytes.  It  is  very  common  to  find 
Large  bubbles  of  air  sharply  defined  within  the  purulent 
contents  of  the  bronchiole.  In  some  Lobules  the  alve- 
olar ducts,  infundibula  and  alveoli  intervening  between 
these  foci  of  leucocytic  pneumonia  arc  almost  uniformly 
filled  with  fibrin  and  polynuclear  leucocytes,  but  in  other 
places  the  formation  of  complete  Layers  of  hyaline  fibrin 
is  in  process.  Bubbles  of  air  arc  often  seen  within  the  al- 
veolar ducts,  and  about  them  is  an  irregular  Layer  of  fibrin 
formed  by  the  penetration  of  air  into  a  channel  previously 
filled  with  a  loose  network  of  fibrin  containing  serum  in  its 
meshes.  The  fibrin  compressed  against  the  walls  of  alve- 
olar duct  and  infundibulum  remains  as  a  compact  Layer  sep- 
arating these  structures  from  the  alveoli  which  project 
Prom  their  walls.  The  bubble  of  air  is  doubtless  later  ab- 
sorbed and  replaced  by  serum,  so  that  many  alveolar  ducts 
are  filled  with  serum  almost  wholly  free  from  cells,  whereas 
alveoli  outside  the  fibrinous  membrane  contain  a  network 
of  fibrin  with  leucocytes  in  greater  or  less  abundance. 

In  association  with  this  fibrinous  pneumonia,  which  has 
been  described,  hyaline  thrombosis  of  the  capillaries  is  not 
uncommon.  This  hyalin  material  within  the  capillaries 
gives  reactions  of  fibrin,  and  in  sections  stained  by  the 
Grram-Weigert  method  for  demonstration  of  fibrin,  these 
thrombosed  vessels  have  the  appearance  of  capillaries  ir- 
regularly injected  with  a  blue  material. 

The  interstitial  tissue  surrounding  consolidated  lobules 
is  often  edematous;  the  lymphatics  are  distended  with 
serum  and  contain  a  moderate  number  of  lymphocytes  and 
polynuclear  leucocytes. 

Among  the  lungs  which  have  been  studied  histologically, 
pneumococcus  has  been  almost  invariably  associated  with 
the  lobular  lesions  which  have  just  been  described,  whether 
hemorrhagic,  leucocytic  or  fibrinous;  the  histologic  changes 
accompanying  infection  of  the  lung  with  streptococcus  will 
be  described  Later.     Pneumococcus  has  been  cultivated  from 


PATHOLOGY  AND  BACTERIOLOGY    KOLLOVVINO    INFLUENZA      L85 


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L86      PNEUMONIAS  AXli   [NFECTIONS  OF   RESPIRATOR'S  TRACT 

the  consolidated  Lung  and  is  found  in  section  of  the  lung. 
B.  influenzae  is  Pound  in  cultures  made  from  the  bronchi. 
Table  WWII  I  includes  those  instances  in  which  the 
histology  of  the  consolidated  lung  accords  with  the  descrip- 
tion given  above. 

Pneumococcus  was  found  in  all  but  2  instances,  and  in 
one  of  these  (Autopsy  336)  the  only  culture  was  from  the, 
heart's  blood  and  in  the  other  (Autopsy  498)  cultures  were 
unsatisfactory  because  proper  media  were  not  obtainable. 
Pneumococci  of  Types  I,  II,  II  atypical,  III  and  IV  are  rep- 
resented in  the  list.  B.  influenzae  has  been  found  in  a  con- 
siderable number  of  instances  in  which  cultures  have  been 
made  from  the  lung  and  in  every  instance  in  which  cultures 
have  been  made  from  the  bronchi.  Staphylococci  are  often 
found  in  the  bronchi,  but  in  most  instances  they  do  not 
penetrate  into  the  lung. 

Another  group  of  cases  of  lobular  pneumonia  are  im- 
portant because  in  association  with  necrosis  of  lung  tissue 
recognized  by  tlie  microscope  hemolytic  streptococci  have 
been  found  in  the  lungs.  In  such  instances  serum  is  abun- 
dant and  polynuclear  leucocytes  are  relatively  scant 
though  their  distribution  varies  considerably;  in  some 
places  leucocytes  are  fairly  abundant  though  elsewhere  al- 
most absent,  but  this  distribution  bears  no  obvious  relation 
to  the  bronchioles.  In  some  instances  (Autopsies  274  and 
487)  red  blood  corpuscles  are  numerous  but  in  others  (Au- 
topsies 27o  and  312)  they  are  inconspicuous.  The  char- 
acteristic feature  of  the  lesion  is  the  occurrence  of  patches 
of  necrosis  within  which  the  nuclei  both  of  exudate  and  of 
alveolar  walls  have  partially  or  completely  disappeared. 
In  these  areas  of  necrosis  short  chains  of  streptococci  are 
found  in  immense  number  whereas  in  living  tissue  they  are 
present  in  moderate  number.  There  has  been  a  relatively 
inactive  inflammatory  reaction,  great  proliferation  of 
streptococci  and  necrosis  of  invaded  tissue.  The  bacte- 
riology  of  instances  of  lobular  pneumonia  with  necrosis  is 
shown' in  Table  WXFX, 


PATHOLOGY  AND  BACTIC1UOLOO  V    KOLLOWf  MO    IXI'U'KXZA      L87 


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!  ss      PNEUMONIAS  AXh   INFECTIONS  OE   RESPIRATOR'S  TRACT 

Lobular  pneumonia,  in  some  of  these  instances  al  Least, 
has  been  caused  primarily  by  pneumococci;  necrosis  lias 
been  the  result  of  secondary  invasion  by  streptococci.  In 
Autopsy  -7o  Pneumococcus  IV  lias  been  obtained  from  the 
blood,  but  in  the  presence  of  streptococci  has  presumably 
disappeared  from  the  lung  and  bronchus.  In  the  case  rep- 
resented by  Autopsy  274,  Pneumococcus  IV  lias  been  found 
in  the  sputum  live  days  before  death  at  the  onset  of  pneu- 
monia, but  at  this  time  no  hemolytic  streptococci  have  been 
Pound.  In  the  case  represented  by  Autopsy  312,  Pneumo- 
coccus IV,  B.  influenzae  and  a  Pew  colonies  of  hemolytic 
streptococci  have  been  obtained  from  the  sputum  two  days 
after  recognition  of  pneumonia  and  five  days  before  death. 

The  hemorrhagic  and  edematous  consolidation  of  the 
early  pulmonary  lesions  of  influenzal  pneumonia  is  their 
most  distinctive  feature.  Red  confluent  lobular  pneumonia 
is  frequently  found  in  those  who  have  died  within  the  first 
week  following  the  onset  of  influenza.  The  lungs  are  vol- 
uminous and  heavy  and  may  weigh  as  much  as  1,500  grams; 
the  pleura  which  overlies  the  consolidated  area  is  blue  or 
plum  colored  and  usually  shows  scant  if  any  evidence  of 
pleurisy.  Scattered  patches  of  consolidation  are  accu- 
rately limited  to  lobules,  but  in  addition  there  are  large 
areas  often  involving  the  greater  part  of  the  lobes  and  not 
infrequently  situated  in  the  lowermost  part  of  the  lower 
lobes.  This  confluent  consolidation  may  be  obviously  lim- 
ited by  lobule  boundaries.  The  consolidated  tissue  is  deep 
red  and  laxly  consolidated;  red  serous  fluid  escapes  from 
the  cut  surface.  The  lesion  not  infrequently  occurs  in  as- 
sociation with  hemorrhagic  peribronchiolar  pneumonia. 

The  histology  of  this  confluent  lesion  has  been  studied 
in  Autopsies  242,  244,  303,  336,  464,  474  and  506.  The  his- 
tology varies,  because,  in  some  instances,  leucocytes,  in 
other  instances,  fibrin,  is  abundant,  but  the  presence  of  red 
blood  corpuscles  in  large  number  within  the  alveoli  gives 
a  red  color  to  the  consolidated  tissue.     In  these  cases  pneu- 


PATHOLOGY  AND   BACTERIOLOGY    FOLLOWING    INI'U'KXZA      L89 

mococci,  associated  in  the  lungs  or  in  the  bronchi  with  I'». 
influenzae,  have  been  the  cause  of  pneumonia.  In  two  au- 
topsies studied  histologically  (Autopsies  274  and  478)  there 
was  red  lobular  and  confluent  pneumonia  and  the  blood  and 
lungs  contain  hemolytic  streptococci  demonstrated  by  cul- 
tures; microscopic  examination  showed  the  presence  of  a 
widespread  necrosis  of  the  lung  tissue. 

In  the  group  of  autopsies  in  Table  XL  tliere  was  red  con- 
fluent lobular  pneumonia.  These  autopsies  are  separated 
from  those  just  cited  because  there  was  no  histologic  ex- 
amination of  the  tissue. 

Table  XL 


NO.  OP 

BACTERIOLOGY 

OP 

BACTERIOLOGY    OF                    BACTERIOLOGY    OP 

TOPSY 

HEART 'S     BLOOD 

LUNGS                                         BRONCHUS 

289 

Fneum.  IV 

Pneum.   IV          Pneum.  IV,  B.  inf.,  staph. 

297 

Pneum.   IV,   B.   inf.  Pneum.  IV,  B.  inf.,  S.  hem. 
(a  few) 

306 

339 

Fneum.  IV 

364 

S.  hem. 

418 

Pneum.  atyp. 

II 

Pneum.    atyp.    II, 
B.  inf.,  S.  vir. 

424 

Pneum.    IV. 

This  group  of  autopsies  confirms  the  view  that  the  red 
confluent  lobular  pneumonia  is  caused  by  pneumococci  in 
association  with  B.  influenzae.  Hemolytic  streptococci  may 
invade  secondarily.  In  Autopsy  297  a  few  hemolytic  strep- 
tococci were  found  in  the  bronchus  but  apparently  had  not 
entered  the  lungs.  In  the  absence  of  histologic  examina- 
tion it  is  not  possible  to  determine  if  the  invasion  of  hemo- 
lytic streptococcus  (in  Autopsy  364)  has  caused  necrosis  of 
the  pneumonic  tissue. 

Peribronchial  Hemorrhage  and  Pneumonia 

In  a  considerable  number  of  instances,  namely,  in  19  au- 
topsies, hemorrhage  about  the  small  bronchi  has  been  rec- 
ognizable upon  gross  examination  of  the  lung.  A  conspicu- 
ous zone  of  hemorrhage  2  or  3  mm.  in  thickness  surrounds 


190     PNEUMONIAS  ANIi   [NFECTIONS  OF   RESPIRATORS   TRACT 

small  (with  qo  cartilage)  often  dilated  bronchi  and  on  lon- 
gitudinal section  may  be  tracted  for  a  considerable  distance 
along  the  bronchus  I  Fig.  7).  In  many  additional  instances 
peribronchial  hemorrhage  has  been  round  by  microscopic 
examination.  In  sonic  instances  the  peribronchial  zone  of 
hemorrhage  is  firmer  than  the  tissue  elsewhere  and  it  is 
occasionally  difficult  to  determine  whether  the  lesion  is 
hemorrhage  or  pneumonia.     In  7  instances  Prank  rod  con- 


Fig.   7. — Bronchopneumonia  with  purulent  bronchitis  and  peribronchial  hemorrhage. 

solidation  of  peribronchial  tissue  was  recognized  at  au- 
topsy; this  lesion  will  be  considered  later  under  peribron- 
chial pneumonia.  Hemorrhage  about  bronchi,  like  other 
evidences  of  severe  injury  to  bronchi  following  influenza, 
is  more  frequently  found  in  the  lowermost  parts  of  the 
lungs  than  elsewhere.  It  is  invariably  associated  with 
severe  bronchitis;  the    bronchi    have    contained    purulent 


PATHOLOGY   AND  BACTERIOLOGY    FOLLOWING    I  X  I'M  '  KXZA      11)1 

fluid  in  15  of  L9  instances  of  peribronchial  hemorrhage  and 
in  10  instances  the  lesion  has  been  associated  with  dilata- 
tion of  the  bronchi. 

Microscopic  examination  furnishes  further  evidence  of 
the  severity  of  the  bronchial  changes  which  have  broughl 
about  hemorrhage  into  the  surrounding  alveoli.  The  lumen 
of  the  bronchus  contains  blood  and  leucocytes;  the  epithe- 
lium is  sometimes  raised  in  places  from  the  underlying 
basement  membrane  by  blood;  blood  vessels  of  the  bron- 
chial wall  are  engorged,  and  there  is  hemorrhage  into  the 
tissue  of  the  bronchus.  More  frequently  the  bronchial  epi- 
thelium is  completely  lost  and  the  denuded  surface  is  often 
covered  by  a  layer  of  fibrin  intimately  adherent  to  the  in- 
flamed mucosa.  Transitions  between  simple  hemorrhage 
and  pneumonia  are  found,  polynuclear  leucocytes  being 
mingled  with  red  blood  corpuscles.  In  several  instances 
the  alveoli  in  immediate  contact  with  the  bronchial  wall 
have  contained  fibrin,  whereas  those  in  the  surrounding- 
zone  have  contained  blood. 

Bacteria  found  in  the  bronchi  in  10  instances  of  peri- 
bronchial hemorrhage  have  been  as  follows; 

Staphylococci    1 

B.  influenzae,   pneumococci    1 

' '            S.  hemolyticus  2 

pneumococci,    staphylococci    1 

S.  hemolyticus,  staphylococci   4 

No  organism  found 1 

The  high  incidence  of  B.  influenzae  and  the  frequent  as- 
sociation of  B.  influenza?  and  hemolytic  streptococci  are 
noteworthy.  The  instance  in  which  no  organisms  were 
found  is  probably  due  to  a  defect  in  media  and  should  per- 
haps be  excluded  from  the  list. 

The  percentage  incidence  of  pneumococci,  hemolytic 
streptococci,  staphylococci  and  B.  influenzae  in  the  bronchus, 
lungs  and  blood  of  the  heart  is  an  index  of  the  facility  with 
which  these  microorganisms  penetrate  internal  organs 
when  the  bronchi  are  the  site  of  this  hemorrhagic  lesion. 


192      PNEUMONIAS  AND   INFECTIONS  OF   RESPIRATOR'S  TRACT 


Table   \u 


X 

- 

O     H 

_•    5 
-    _ 
y.  Z 

PNEUMOCOCC1 

HEMOLYTIC 
STREPTOCOCCI 

ST  \l'll\  LO- 
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w     ° 

£    p. 

Bronchus 

Lung 

Blood 

10 
L3 

17 

>> 

4 
1 

120.0 
30.8 
23.5 

6 
7 
9 

60.0 
53.8 

52.9 

6 
3 

(50.0 
23.1 

8 
5 

80.0 
38.5 

When  these  figures  are  compared  with  those  for  ;ill  forms 
of  bronchitis  no  very  noteworthy  differences  are  found ; 
the  incidence  of  pneumococci  here  is  less  and  that  of  hemo- 
lytic streptococci  greater.  In  association  with  the  severe 
changes  present  in  the  bronchi,  hemolytic  streptococci 
which  enter  the  lungs  almost  invariably  find  their  way  into 
t  he  blood. 

Tn  6*  instances  there  lias  been  frank  pneumonic  consolida- 
tion limited  to  a  zone  encircling  small  and  medium-sized 
bronchi  which  have  often  been  obviously  dilated.  On  cross 
section  these  patches  of  pneumonia  are  circular,  from  1  to 
2  cm.  in  diameter  and  each  contains  a  bronclius  at  its  center. 
When  the  bronchus  is  cut  longitudinally  it  is  evident  that 
pneumonic  consolidation  forms  a  cylindrical  sheath  about 
the  tube.  The  consolidation  varies  in  color  from  red  to 
grayish  red.  In  one  instance  (Autopsy  253)  the  consoli- 
dated tissue  has  formed  a  gray  zone  in  contact  with  the 
bronchus  and  is  red  in  a  peripheral  zone;  microscopic  ex- 
amination shows  that  the  alveoli  about  the  bronclius  con- 
tain fibrin,  whereas  those  at  a  greater  distance  contain  red 
blood  corpuscles.  In  this  instance,  the  associated  pneu- 
monia in  another  part  of  the  lung  has  been  somewhat 
anomalous  and  has  had  characters  both  of  lobar  and  bron- 

ehopneun ia.  for  scattered  in  the  left  lung  there  have  been 

patches  of  firm  consolidation  not  more  than  2  cm.  across. 
The  smaller  of  these  patches  are  deep  vrd,  but  the  larger 
are  coarsely  granular  and  gray  in  the  center.    The  patchy 


PATHOLOGY  AND   BACTERIOLOGY    FOLLOWING    I  X  FH  'K.\7 A      1!).'! 

character  of  the  lesion  has  suggested  bronchopneumonia, 
but  the  coarse  granulation  on  section  and  the  presence  of 
fibrinous  plugs  within  the  small  bronchi  have  presented  a 
close  resemblance  to  lobar  pneumonia.  This  autopsy  is 
one  of  the  few  instances  in  which  Pneumococcus  II  has  been 
found,  Pneumococcus  II  being  present  in  blood  and  lungs, 
B.  influenzae,  in  lungs  and  bronchi.  In  2  additional  in 
stances  (Autopsies  374  and  392)  peribronchial  pneumonia, 
recognizable  at  autopsy,  has  been  associated  with  consoli- 
dation having  the  characters  of  lobar  pneumonia.  In  one 
instance,  Autopsy  374,  the  right  lung  has  contained  two 
patches  of  firm,  mottled  red  and  pinkish  red  coarsely  gran- 
ular consolidation  each  about  6  cm.  across,  one  situated  in 
the  upper  lobe  and  the  other  in  the  lower  lobe.  Elsewhere 
in  the  lung,  in  definite  relation  to  dilated  bronchi,  occur 
patches  of  firm,  red,  coarsely  granular  consolidation  from 
1  to  1.5  cm.  in  diameter  when  cut  transversely.  The  bron- 
chus in  the  center  has  contained  purulent  fluid.  In  the  op- 
posite lung  similar  consolidation  has  been  limited  to  zones 
about  dilated  bronchi  which  contain  purulent  fluid.  Pneu- 
mococcus IV  has  been  obtained  from  the  blood  of  the  heart. 
The  peribronchial  pneumonia  which  has  been  described 
occurs  in  association  with  evidence  of  profound  injury  to 
the  bronchial  wall.  In  5  of  6  instances  purulent  bronchitis 
has  been  found  at  autopsy;  in  half  of  these  instances  bron- 
chiectasis has  been  noted.  The  epithelium  of  the  bronchus 
has  been  found  separated  from  the  underlying  tissue  by  se- 
rous exudate,  blood  and  leucocytes ;  epithelial  cells  undergo 
necrosis  and  disappear,  the  denuded  surface  being  covered 
by  fibrin.  Necrosis  extends  a  varying  depth  into  the  wall 
of  the  bronchus ;  blood  vessels  are  engorged,  and  there  is 
in  some  instances  hemorrhage  throughout  the  wall  of  the 
bronchus. 

The  character  of  the  exudate  in  the  alveoli  surrounding 
the  bronchus  differs  considerably  in  different  instances. 
In  some  instances  (Autopsies  374  and  392)  red  blood  cor- 


L94      PNEUMONIAS  A\"D   [NFECTIONS  OF  RESPIRATORY  TRACT 

puscles  are  predominant  in  the  alveoli  in  contacl  with  the 
bronchia]  wall,  whereas  in  a  peripheral  zone  polynuclear 
leucocytes  are  more  abundant.  In  other  instances  (Autop- 
sies 253  and  402)  alveoli  next  the  bronchial  wall  contain 
abundant  fibrin  and  these  are  surrounded  by  a  zone  in 
which  the  alveoli  are  filled  wil li  blood. 

Peribronchial  pneumonia  is  the  result  of  the  direct  ex- 
tension of  the  inflammatory  process  through  the  wall  of  the 
bronchus;  it  occurs  when  the  epithelium  of  the  bronchus  is 
destroyed  and  the  underlying  tissues  are  injured,  but 
may  be  present  in  a  wide  encircling  /one  even  when 
the  lesion  has  not  penetrated  the  bronchial  wall.  The  dis- 
tribution of  the  pneumonia  demonstrates  very  clearly  that 
the  inflammatory  process  does  not  reach  the  affected  peri- 
bronchial alveoli  by  way  of  the  bronchioles  tributary  to  the 
bronchus. 

The  bacteriology  of  these  instances  of  peribronchial 
pneumonia  is  noteworthy.     (Table  XLTT.) 


Tabu:  XLIT 


AUTOPSY 

BLOOD 

LTTNG 

BRONCHUS 

253 

Pneum.  II 

Pneum.  II,  B.  inf. 

Staph.,   B.   inf. 

374 

Pneum.  IV 

387 

Pneum.  II,  S.  hem. 

Pneum.  II,  staph.. 

Pneum.  II,   S.  horn., 

B.  inf. 

staph.,  B.  inf., 

392 

Pneum.  II 

402 

Pneum.  IV,  S.  hem. 

424 

? 

Pneum.  IV 

Pneumococcus  has  been  found  in  every  instance  either  in 
the  lungs  or  blood.  Pneumococcus  IT,  which  has  been  un- 
common with  the  pneumonia  following  influenza  at  Camp 
Pike  and  has  occurred  only  ten  times  in  more  than  200 
autopsies,  has  been  present  in  one-half  of  these  cases.  The 
constant  association  of  the  lesion  with  pneumococcus  is 
particularly  significant  when  a  comparison  is  made  between 
the  incidence  of  pneumococcus  with  peribronchial  hemor- 
rhage, on  the  one  hand,  and'peribronchial  pneumonia  on  the 
other;  pneumococcus  has  been  present  in  less  than  a  third 


PATHOLOGY  AND  BACTERIOLOGY   FOLLOWING    I  X  PL!  'KXZA      195 

of  the  instances  of  hemorrhage  but  in  all  instances  of  pneu- 
monia. 

In  addition  to  the  instances  in  which  gross  peribronchial 
consolidation  has  been  noted  at  autopsy,  microscopic  ex- 
amination has  demonstrated  the  presence  of  fibrinous  pneu- 
monia surrounding-  bronchi  in  a  considerable  number  of 
autopsies.  In  a  zone  encircling-  small  bronchi  (with  no 
cartilage)  alveoli  are  rilled  by  plugs  of  dense  fibrin  ( Pig. 
20)  containing  in  variable  number  polynuclear  leucocytes 
and  mononuclear  cells.  The  width  of  the  zone  is  often 
equal  or  greater  than  the  diameter  of  the  bronchus.  Alve- 
oli outside  the  zone  of  fibrinous  inflammation  may  contain 
red  blood  corpuscles  or  serum,  and  desquamated  epithelial 
cells  are  often  abundant. 

Of  21  instances  of  peribronchial  fibrinous  pneumonia  20 
were  associated  with  purulent  bronchitis.  Further  evi- 
dence of  the  relation  of  the  lesion  to  profound  injury  to 
the  bronchi  is  its  association  with  bronchiectasis  in  17  in- 
stances. 

Peribronchial  fibrinous  pneumonia,  like  other  lesions  en- 
circling the  small  bronchi,  bears  a  direct  relation  to  the 
severity  of  microscopic  changes  in  the  bronchus.  The  epi- 
thelium of  the  bronchus  is  either  partially  or  completely 
lost.  Occasionally  epithelium  is  raised  by  hemorrhage  or 
leucocytes  from  the  underlying  tissue  but  more  frequently 
it  is  wholly  lost  and  the  surface  is  covered  by  a  layer  of 
fibrin.  In  the  early  stages  of  the  lesion,  polynuclear  leuco- 
cytes may  be  numerous  throughout  the  bronchial  wall,  in- 
dicating that  the  inflammatory  irritant  within  the  lumen  is 
affecting  the  entire  wall  and  extending  its  influence  to  the 
surrounding  pulmonary  tissue.  Later  lymphoid  and  plas- 
ma cells  are  more  abundant  than  polynuclear  leucocytes. 
Coagulative  necrosis  and  disintegration  of  the  bronchial 
wall,  proceeding  from  the  inner  surface  outward,  may  ex- 
tend more  or  less  deeply,  and  fibrinous  inflammation  of 
adjacent  alveoli  is  often  more  extensive  about  that  segment 


l!)li      PNEUMONIAS  AND   INFECTIONS  OF   RESPIRATORS   TRACT 

of  ilif  bronchus  which  shows  the  greatesl  change.  In  some 
instances  segments  of  the  bronchial  wall  or  even  the  entire 
wall  has  disappeared,  so  thai  alveoli  containing  fibrin  form 
part  of  the  wall  of  the  cavity  thus  formed.  When  bron- 
chiectasis lias  occurred,  there  arc  often  fissures  from  the 
lumen  through  the  entire  wall  extending  into  the  surround- 
ing lung  tissue:  hen*  fibrinous  pneumonia  is  particularly 
conspicuous,  occurring  in  a  zone  about  the  edges  of  the 
defect.  This  deposition  of  fibrin  within  the  alveoli  adja- 
cent to  the  injury  doubtless  has  a  pari  in  limiting  the  dis- 
tribution  of  bacterial  infection.  Nevertheless  breaks  in  the 
continuity  of  the  bronchial  wall  are  no1  essential  to  the 
production  of  the  lesion  and  the  irritant,  which  is  respon- 
sible for  the  lesion,  may  penetrate  through  the  bronchial 
wall  to  surrounding  alveoli  and  from  alveoli  to  other  al- 
veoli immediately  adjacent. 

Willi  this  peribronchial  pneumonia  the  smallest  bronchi 
are  distended  with  pus  and  their  walls  are  infiltrated  with 
polynuclear  leucocytes,  lymphoid  and  plasma  cells.  In  a 
broad  zone  encircling  the  bronchus  the  alveoli  are  tilled 
with  plugs  of  fibrin.  Bronchioles  are  similarly  distended 
with  polynuclear  leucocytes;  the  alveoli  which  occur  upon 
the  wall  of  the  bronchiole  are  often  limited  to  one  side  of 
lie  wall  and  are  filled  with  fibrin.  This  fibrin  occasionally 
projects  into  the  lumen  of  the  bronchiole  and  forms  a  con- 
tinuous layer  in  contact  with  the  wall  on  the  same  side. 
The  alveolar  duet  and  inl'undibulum  are  distended  with 
polynuclear  leucocytes.  The  alveoli  upon  the  wall  of  the 
alveolar  duct  and  upon  the  proximal  part  of  the  infundib- 
uluni  are  filled  with  fibrin.  The  bronchus,  bronchiole, 
alveolar  duct  and  part  of  the  infundibulum  are  thus  sur- 
rounded by  a  continuous  /-one  of  alveoli  containing  fibrin. 
The  alveoli  about  the  distal  part  of  the  infundibulum  may 
be  filled  with  polynuclear  leucocytes.  Lung  tissue  between 
adjacent  zones  of  fibrinous  pneumonia  may  contain  serum 
and  desquamated  epithelial  cells. 


PATHOLOGY  AND  BACTERIOLOGY    FOLLOWING    [INFLUENZA      IDT 

Organization  of  peribronchial  fibrin  was  found  in  LO 
of  the  22  autopsies  in  which  peribronchial  fibrinous  pneu- 
monia had  been  found.  Fibroblasts  have  invaded  the  fibrin 
and  newly  formed  capillaries  have  p.enetrated  into  it.  In 
some  instances  the  iiiteralveolar  septa  are  thickened  and 
infiltrated  with  lymphoid  and  plasma  cells,  and  in  7  in- 
stances there  was  chronic  pneumonia  with  thickening  and 
mononuclear  infiltration  of  the  interstitial  tissue  about  the 
bronchi  and  blood  vessels,  and  elsewhere.  The  duration 
of  the  fatal  illness  in  12  instances  with  no  organization  was 
usualty  from  ten  days  to  two  weeks,  though  in  3  instances 
there  was  no  organization  although  the  respiratory  disease 
had  lasted  from  seventeen  to  nineteen  days  (average  dura- 
tion with  no  organization,  13.5  days).  The  duration  of 
illness  in  10  instances  with  organization  of  fibrin  was 
slightly  less  than  three  weeks  (average  18.9  days).  These 
figures  do  not  accurately  represent  the  duration  of  pneu- 
monia which  usually  develops  after  a  period  of  several  days 
following  onset  of  influenza. 

This  group  of  instances  of  peribronchial  fibrinous  pneu- 
monia has  offered  an  opportunity  to  study  the  bacteriology 
of  pneumonia  with  organization  and  to  determine  if  it  pre- 
sents any  unusual  characters.  The  bacteriology  of  autop- 
sies with  peribronchial  fibrinous  pneumonia  with  no  or- 
ganization is  shown  in  Table  XLIII: 


Table  XLIII 


AUTOPSY 

BLOOD 

LUNG 

BRONCHI'S 

289 
372 
376 

Pneum.  IV 

Pneum.  IV 

Pneum.'  IV,  B.  inf.,  staph. 

S.   hem. 

S>.  hem. 

S.  hem.,  B.  inf.,  S.  aur. 

409 

0 

410 

S.  hem.,  B.  inf.  S.  aur. 

412 

Pneum.  II 

Pneum.  II,  B.  inf. 

420 

S.  hem. 

S.  hem.,  B.  inf.  S.  aur. 

423 

S.  hem. 

8.  hem.,  B.  inf. 

440 

0 

B.  inf.,  S.  aur. 

B.  inf.,  S.   aur. 

448 

0 

0 

0 

482 

0 

B.  inf.,  Pneum.  IV 

B.    inf..    Pneum.    IV, 
S.    hem. 

489 

0 

Pneum.  IAT,  B.  inf. 

Pneum.  IV,  B.  inf. 

198      PNEUMONIAS  AXIi   INFECTIONS  OF   RESPIRATORS   TRACT 

The  bacteriology  of  instances  of  peribronchial  fibrinous 
pneumonia  with  organization  of  the  Lntraalveolar  fibrin  is 
shown  in  Table  XL1 V  : 


Table  XLIV 

AUTOPSY 

BLOOD 

LUNG 

BRONCHUS 

283 

Pneum.  1  V 

Staph.,  B.   inf. 

R.  inf.,  Pneum.  IV,  st; 

iph 

291 

0 

0 

1'..   inf.,  staph. 

ig 

0 

•IIP 

0 

Pneum.   [I,  B.  inf. 

Pneum.  1 1,  B.  inf. 

IL'1 

S.   hem. 

Pneum.  IV,  S.  hem. 

422 

0 

Pneum.  Tl  atyp.,  B.  inf. 

+25 

S.   hem. 

s.  hem.,  B.  inf.,  S.  alb. 

433 

0 

s.  hem.,  B.  inf.,  S.  aur. 

460 

S.  hem. 

S.  hem.,  B.  inf. 

s.  hem.,  B.  inf.,  staph. 

463 

0 

B.    inf.,   staph. 

!'..  inf.,  staph.,  Pneum. 

rv 

B.  influenzae  lias  been  presenl  in  the  bronchi  in  every  in- 
stance save  one  in  which  cultures  have  been  made,  and  it 
is  probable  thai  in  this  exceptional  instance  cultures  have 
remained  sterile  because  the  media  employed  have  been  de- 
fective'. The  incidence  of  B.  influenza'  in  the  lung  has  been 
unusually  high  both  with  and  without  organization  (66.7 
per  cent  with  no  organization;  77.8  per  cent  with  organ- 
ization). Streptococci  and  staphylococci  have  been  found 
in  a  considerable  proportion  of  all  instances  of  peribron- 
chial fibrinous  pneumonia,  but  there  has  been  no  notable 
preponderance  of  these  microorganisms  when  organiza- 
tion has  occurred.  Organization  has  been  present  in  in- 
stances in  which  pneumonia  is  referable  to  pneumococcus 
associated  with  B.  influenzae  and  unaccompanied  by  either 
streptococci  or  staphylococci  (Autopsies  419  and  422). 
Wadsworth1  found  no  organization  after  inoculation  of  the 
lungs  of  dogs  with  pneumococcus  or  with  staphylococcus 
alone,  but  produced  organization  when  he  inoculated  an- 
imals with  both  microorganisms. 

Injury  to  bronchi  produced  in  part  at  least  by  B.  in- 
fluenzae exposes  the  bronchi  and  lung  tissue  to  repeated 
infection  with  a  variety  of  microorganisms;  absorption  of 

'Wadsworth,    A.    B.:     A    Study    of   Organizating   Pneumonia.   Jour.    Med.    Research,    1918, 
xxxix,    147. 


PATHOLOGY  AND   BACTERIOLOGY    FOLLOWING    [NFLUENZA      190 

fibrin  an<l  regeneration  of  alveolar  epithelium  are  pre- 
vented, resolution  fails  to  occur  and  organization  of  fibrin 
follows. 

Suppurative  Pneumonia  With  Necrosis  and  Abscess 
Formation 

Three  varieties  of  suppurative  pneumonia  have  occurred 
in  association  with  influenza. 

A.  Necrosis  and  suppuration  with  formation  of  one  or 
several  abscesses  usually  below  the  pleura  and  almost  in- 
variably caused  by  hemolytic  streptococci. 

B.  Interstitial  suppurative  pneumonia  caused  by  hemo- 
lytic streptococcus. 

C.  Multiple  abscesses  in  clusters  caused  by  staphylococci. 

Suppurative  pneumonia  with  necrosis  and  abscess  for- 
mation will  be  discussed  in  this  section.  Pulmonary  ab- 
scesses which  occurred  in  43  autopsies  may  be  included  in 
this  group ;  in  4  of  these  autopsies  abscess  and  interstitial 
suppurative  pneumonia  occurred  in  the  same  individual. 
These  abscesses  were  much  more  frequently  situated  in  the 
lower  than  in  the  upper  lobes  and  more  often  in  the  right 
than  in  the  left  lung. .  In  most  instances  there  was  one  or 
several  abscesses  situated  below  the  pleura  of  one  lobe; 
occasionally  abscesses  occurred  in  two  lobes  of  the  same 
lung  or  in  both  lungs.  The  distribution  was  as  follows : 
Abscess  in  only  one  lung  occurred  in  right  upper  lobe  in 
6  autopsies;  middle  lobe,  3;  lower  lobe,  15;  left  upper  lobe, 
2;  lower  lobe,  16.  Abscesses  occurred  in  both  right  and 
left  lower  lobes,  twice.  The  usual  situation  was  at  the 
lower  and  posterior  part  of  the  lower  lobe  at  or  near  the 
basal  edge,  less  frequently  below  the  posterior  border  or 
upon  the  basal  surface  of  the  lobe.  These  abscesses  in 
almost  every  instance  were  found  immediately  below  the 
pleural  surface,  so  that  they  appeared  upon  the  pleura 
as  opaque  yellow  spots  usually  surrounded  by  narrow 
zones  of  hemorrhage.     In  one  instance  (Autopsy  376)  the 


PNEUMONIAS  A  N  1 «   I  X  IT.CTh  >  Xs  OTT   RESPIRATOR'S   TRACT 

abscess  cavity  was  separated  from  the  pl<  ural  cavity  by 
remains  i  t'  the  pleura  which  was  as  thin  as  1  issue  paper  and 
in  other  instances  perforation  had  occurred  (Fig.  9).  En 
Autopsy  480  the  abscess  cavity  which  had  perforated  the 
pleura  was  in  five  communication  with  a  bronchus  of  me- 
dium size. 

In  most  instances  of  suppurative  pneumonia  there  have 
been  associated  lesions  of  bronchopneumonia  which  have 
been  peribronchiolar,  hemorrhagic  or  lobular  and  have  cx- 
hibited  no  unusual  characters.  The  abscess  or  abscesses 
are  situated  within  an  area  of  pneumonic  consolidation 
which  is  not  limited  by  lobule  boundaries  and  has  no1  the 
characters  of  bronchopneumonic  consolidation.  In  some 
instances  this  consolidation  is  limited  to  a  '/cue  immediately 
about  the  abscess,  but  often  it  involves  the  greater  part  of 
a  lobe.  The  tissue  is  laxly  consolidated  and  flabby;  on  sec- 
tion it  has  a  dull,  conspicuously  cloudy  appearance  and  is 
grayish  red,  pinkish  gray  or  gray;  it  is  homogeneous  or 
very  finely  granular.  Turbid  gray  fluid,  which  sometimes 
resembles  thin  pus,  oozes  from  the  cut  surface1. 

Widespread  necrosis  of  tissue  is  not  infrequently  a  con- 
spicuous feature  of  this  pyogenic  pneumonia  (Fig.  8). 
Upon  a  cloudy  gray  background  of  consolidation  are  nu- 
merous opaque  yellowish  gray  or  yellow  patches,  occasion- 
ally 2  or  3  cm.  across,  giving  a  mottled  character  to  the 
cut  surface.  Upon  the  pleura  these  necrotic  patches  ap- 
pear as  dull  opaque  yellow  spots.  They  may  be  sur- 
rounded by  a  zone  of  hemorrhage.  The  opaque  material 
is  a1  first  firm  but  may  undergo  softening,  becoming  semi- 
solid and  finally  purulent.  Necrotic  patches  may  be  scat- 
tered throughout  a  lobe,  but  fully  formed  abscesses  are  with 
few  exceptions  immediately  below  the  pleura  (Fig.  9). 

The  duration  of  illness  in  cases  of  pneumonia  with  ab- 
scess  varied  from  a  week-  or  less  (11  instances)  to  more 
than  four  weeks.  The  duration  of  the  greater  number  of 
cases   (17  instances)  was  between  one  and  two  weeks.     In 


PATHOLOGY  AND  BACTERIOLOGY  FOLLOWING    [NFLTJENZA     201 


Fig.    8. — Streptococcus  pneumonia  with   massive   necrosis.     Autopsy   354. 


202     PNEUMONIAS  AXD  INFECTIONS  OF  RESPIRATOR'S  TRACT 


Fig.  9. — Abscess  below  pleura  with  perforation  caused  by  hemolytic  streptococci.  Heal- 
ing suppurative  interstitial  pneumonia  indicated  by  yellowish  gray  lines  marking  inter- 
lobular septa  at  base   of  lower   lobe.     Autopsy   474;    right   lung.      (See   left  lung,   Fig.    10.) 


PATHOLOGY  AND  BACTERIOLOGY   FOLLOWING    INFLUENZA     203 


one  instance  onset  occurred  with  symptoms  of  influenza, 
pneumonia  was  recognized  two  days  later,  and  death  oc- 
curred only  four  days  after  the  onset  of  illness.  When  the 
duration  of  the  illness  was  less  than  a  week  the  symptoms 
of  onset  were  in  some  instances  those  of  pneumonia. 

Table  XLV  shows  the  incidence  of  pneumococcus,  S.  hem- 
olyticus,  staphylococcus  and  B.  influenzae  in  instances  of 
suppurative  pneumonia  with  abscess  formation,  4  instances 
of  abscess  with  interstitial  suppurative  pneumonia  being 
excluded : 

Table  XLV 


O     Eh 

PNEUMOCOCCI 

HEMOLYTIC 
STREPTOCOCCI 

STAPHYLO- 
COCCI 

B.  INFLUENZAE 

H 

Eh 

O     o 

£     Ph 

Z     > 

O     H 

P3     W 
W      O 

Ph       Ph 

> 

9   ° 

g      Ph 

£    > 

U     Eh 

P3     M 
W     O 

Ph      Ph 

> 
O     o 

%       Ph 

to  oi  1  PER  CENT 
bs  b     POSITIVE 

> 
Eh 

s  ° 

£       Ph 

PER  CENT 
POSITIVE 

Bronchus 

Lung 

Blood 

24 
36 
37 

5 
9 
6 

20.8 
25.0 
16.2 

22 
30 
31 

91.6 
83.3 

83.8 

12 
14 

18 
8 

75.0 
22.2 

In  over  80  per  cent  of  instances  of  pulmonary  abscess 
hemolytic  streptococcus  has  been  found  in  blood,  lungs  and 
bronchus  and,  when  cultures  have  been  made,  in  the  in- 
flamed pleural  cavity  as  well.  Streptococci  have  been 
found  in  immense  number  in  sections  from  the  necrotic 
lung  tissue  and  the  abscesses  which  have  been  formed.  It 
is  evident  that  hemolytic  streptococci  have  caused  suppura- 
tive pneumonia  and  death,  being  found  in  the  blood  of  the 
heart  just  as  frequently  as  in  the  lungs  (83  per  cent).  The 
relative  unimportance  of  pneumococci  is  indicated  by  their 
low  incidence  in  the  blood  (16.2  per  cent)  when  compared 
with  that  of  lobar  pneumonia  (65.5  per  cent)  or  of  broncho- 
pneumonia (31.4  per  cent).  B.  influenza^  has  been  found 
in  three-fourths  of  these  autopsies  in  the  bronchus,  but  its 
incidence  in  the  lungs  has  been  much  smaller. 

In  3  instances  of  suppurative  pneumonia  with  abscess 
formation  no  hemolytic  streptococci  were  found ;  they  are 
as  follows: 


204      PNEUMONIAS  AND   INFECTIONS  OF   RESPIRATORY   TRACT 


Autopsy  380. — Bronchopneumonia  with  gray  and  red  Lobular  consolida- 
tion in  right  npper  and  lower  lobes;  peribronchiolar  nodules  of  consoli* 
dation  in  left  lower  lobe;  abscesSj  1.5  cm.  across,  below  the  pleura  of  the 
posterior  border  of  the  lefl  lower  lobe  near  its  base;  fibrinopurulenl  pleu- 
risy ".i1"  c.c.)  on  right  side;  serous  pleurisy  (200  c.c.)  on  left.  Pneumo- 
coccus  HI  was  found  in  cultures  from  the  blood  of  the  heart  from  the  righl 
lung  and  with  B.  influenzae  from  the  righl  pleural  cavity.  No  culture  was 
made  from  the  left  lung  which  contained  the  abscess,  [n  sections  of  the 
abscess  gram  positive  streptococci  in  chains  of    I    to   8   cocci   were   numerous. 

Autopsy  406. — Acute  lobar  pneumonia  with  red  hepatization  of  greater 
part  of  right  lung;  patch  of  consolidation  in  lower  lube  of  left  lung  con- 
taining an  abscess  cavity  2.5  x  L.5  cm.;  localized  seropurulent  pleurisy 
i  .".7.1  <■.<■.<  on  left  side.  Pneumococcus  1 V  was  obtained  from  the  blood  of 
the  heart;  a  culture  from  the  lung  was  contaminated.  Tissue  from  the 
abscess  was  no1   saved  for  histologic  examination. 

Autopsy  416. — Suppurative  pneumonia  with  necrosis  and  abscess  forma- 
tion in  right  lower  lobe;  fibrinous  pleurisy  on  right  side.  Pneumococcus 
IV  was  obtained  from  the  blood,  right  lung  and  right  main  bronchus.  No 
streptococci   were   found   in   sections  from  the  abscess  in   the  right  lung. 

The  foregoing  observations  demonstrate  that  suppura- 
tive pneumonia  with  abscess  formation  following  influenza 
is  with  few  exceptions  caused  by  S.  hemolyticus. 

The  autopsies  (Table  XLVI)  in  which  pneumococci  have 
been  round  in  association  with  hemolytic  streptococci  in  the 
blood  or  lungs  indicate  that  pneumococci  have  had  a  pari 
in  the  production  of  fatal  pneumonia. 

Table  XLVI 


AUTOPSY 

CULTURE  FROM   BLOOD 

CULTURE    FROM    LUNGS 

CULTURE     FROM 
BROXCHUS 

258 

s.   hem. 

S.    hem.,    Pneum.    IV 
B.  inf. 

282 

s.  hem.,  Pneum.  II 

S.  hem.,  Pneum.  II 

s.  hem.,  B.  inf. 
Pneum.  II,  staph. 

345 

S.    hem.,    Pneum,    IT. 
staph. 

378 

Pneum.  atyp.  II 

s.  hem.,  Pneum.  a1  vp 

S.  hem.,  B.  inf., 

II 

Pneum.  atyp.  II 

381 

s.   hem. 

S.    horn.,    Pneum.    TT 
Pneum.  IV,  staph. 

383 

Pneum.  Ill 

S.  hem..  Pneum.  TIT 
B.  inf. 

387 

s.  hem. 

Pneum.   IT,   staph., 

s.  hem.,  pneum., 

B.  inf. 

staph.,  B.  inf. 

These  autopsies,   notably  those   in    which    pneumococci 
have  been  found  in  the  blood,  suggest  that  infection  with 


PATHOLOGY  AND  BACTERIOLOGY  FOLLOWING  I  X  I'M  I  KXZA  205 

pneumococci  has  preceded  suppurative  pneumonia  caused 
by  hemolytic  streptococci.  In  a  small  number  of  instances 
the  sputum  was  examined  in  life  after  onsel  of  pneumonia. 

Table  XLVII 


AUTOPSY 

SPUTUM 

CULTURES  FROM  BLOOD,  LUNGS  AND  BRONCHI'S 

282 
288 
376 

Pne am.  IV.  B.  inf. 
S.   hem.,  B'.  inf. 
(No  S.  hem.,  Oct.  8) 

S.  hem.,  Pneum.  II,  staph.,  B.  inf. 

S.  hem.,  B.  inf. 

8.  hem.,  staph.,  B.  inf.   (Oct.  11) 

In  2  of  these  3  cases  infection  with  hemolytic  streptococ- 
cus occurred  subsequent  to  the  onset  of  pneumonia. 

Several  observations  help  to  explain  the  occurrence  of 
abscess  in  association  with  the  pneumonia  of  influenza. 
The  fissures  which  will  be  described  in  association  with 
bronchiectasis  represent  traumatic  ruptures  of  the  bron- 
chial wall  consequent  upon  weakening  by  necrosis  and  over 
distention.  They  expose  the  injured  bronchial  wall  and 
the  alveolar  tissue  adjacent  to  it  to  infection  by  the  micro- 
organisms contained  within  the  lumen  of  the  inflamed 
bronchus.  Occasionally  a  favorable  microscopic  section 
demonstrates  the  relation  of  pulmonary  necrosis  and  con- 
sequent suppuration  to  injuries  of  the  bronchial  wall. 
Peribronchial  fibrinous  pneumonia  occurs  about  the  bron- 
chi of  which  the  epithelial  lining  has  been  destroyed,  and 
when  a  fissure  penetrates  the  bronchial  wall  fibrinous  pneu- 
monia is  almost  invariably  found  in  a  zone  about  the  tear ; 
it  doubtless  tends  to  limit  the  extension  of  the  process. 
Occasionally,  wide  areas  of  necrosis  occur  within  consoli- 
dated tissue  near  the  site  of  the  fissure  (Autopsy  312  with 
S.  hemolyticus  and  B.  influenzae,  p.  254).  Accumulation  of 
polynuclear  leucocytes  between  living  and  dead  tissue  may 
form  a  line  of  demarcation  (Autopsy  387) ;  finally,  fairly 
large'  irregularly  formed,  abscess  cavities  are  found. 

Necrosis  and  beginning  suppuration  in  contact  with  the 
lumen  of  the  bronchus  will  be  described  in  association  with 
bronchiectasis  (Autopsies  312,  Fig.  24,  and  423,  p.  256).    In 


206      PNEUMONIAS  AX!>   [NFECTIONS  OF   RESPIRATOR'S  TRACT 

the  following  autopsies  upon  individuals  who  have  <lio<l 
with  pulmonary  abscesses,  favorable  microscopic  sections 
have  demonstrated  abscess  formation  in  contact  with  lesions 
which  have  penetrated  the  walls  <>f  small  bronchi.  They 
help  to  explain  the  pathogenesis  of  abscess  in  association 
with  influenza. 

Autopsy  376. —  11.  M.,  white  aged  twenty  four,  a  fireman,  residenl  of 
Oklahoma,  had  been  in  military  service  one  month.  Onset  of  illness  oc- 
curred October  1,  ten  days  before  his  death;  he  was  admitted  to  the  base 
hospital  on  the  fourth  day  of  his  illness  with  the  diagnosis  of  broncho- 
pneumonia. 

Anatomic  Diagnosis.- -Acute  bronchopneumonia  with  patches  of  lobular 
nml  confluent  lobular  consolidation  in  both  Lungs  and  hemorrhagic  peri- 
bronchiolar consolidation  in  right  upper  lobe;  abscess  in  right  upper  lobe 
below  pleura;  librinopurulent  pleurisy  on  right  side;  purulent  bronchitis; 
bronchiectasis  at  base  of  left  lobe. 

An  irregular  abscess.  2x1  cm.,  filled  with  creamy  purulent  fluid  is 
separated  from  the  interlobular  surface  of  the  right  upper  lobe  by  a  thin 
membrane  representing  the  pleura.  The  right  pleural  cavity  contains  200 
c.c.  of  turbid  vellow  fluid  in  which  is  soft  fibrin.  The  bronchi  contain 
purulent  fluid  in  great  abundance.  The  bronchi  at  the  base  of  the  lel'i 
lower  lobe  are  widely  dilated,  so  that  many  small  bronchi  with  no  car- 
tilage  in  their  wall  measure  from  3  to   5  mm.   in   diameter. 

Cultures  show  the  presence  of  hemolytic  streptococci  in  the  blood  of 
the  heart  and  in  three  plates  from  the  lung;  B.  influenzae  and  S.  aureus 
were   found  in   the  left  bronchus. 

The  bronchi  have  wholly  or  partially  lost  their  epithelium  and  there 
is  deep  erosion  of  the  walls.  Cavities  containing  polynuelear  leucocytes 
occur  within  the  alveolar  tissue;  in  some  instances  pus  containing  cav- 
ities are  surrounded  by  alveolar  tissue,  but  in  other  places  it  is  evident 
that  they  have  had  their  origin  in  bronchi.  In  a  short  segment  of  the 
circumference  the  wall  of  the  preexisting  bronchus  is  preserved  and 
consists  of  squamous  epithelium,  vascular  connective  tissue  and  smooth 
muscle.  The  remainder  of  the  bronchus  has  disappeared  and  a  cavity  is 
produced.  The  very  irregular  wall  of  the  cavity  is  formed  by  partially 
destroyed  alveoli  filled  with  fibrin  and  leucocytes. 

Autopsy  387. — C.  M.,  white,  aged  twenty  one,  laborer,  resident  of  Miss- 
issippi, had  been  in  military  service  twenty-one  days.  Illness  began  on 
>'  | >f ember  22,  nineteen  days  before  death,  ami  the  patient  was  admitted 
to  the  hospital  on  the  same  day  with  a  diagnosis  of  bronchitis;  a  diagnosis 
of  bronchopneumonia  was  made  on  October  2,  nine  days  before  death. 
The  leucocytes  on  October  3  numbered  8000  (small  mononuclear,  36  per 
cent;    large   mononuclear,    5    per   cent  ;    polynuelear,   59   per   cent). 


PATHOLOGY  AND  BACTERIOLOGY   FOLLOWING   INFLUENZA     207 

Anatomic  Diagnosis.— Acute  bronchopneumonia  with  consolidation  in 
right  upper  Lobe  and  hemorrhagic  peribronchiolar  consolidation  in  lefl  lower 
lobe;  abscess  below  pleura  in  left  lower  lobe;  purulent  pleurisy  on  both 
sides;  edema  of  mediastinum;  purulent  bronchitis;  bronchiectasis. 

There  is  advanced  bronchiectasis,  and  bronchi  with  no  visible  cartilage 
are  dilated  to  from  4  to  8  nun.  in  diameter;  they  contain  purulent  fluid 
which  wells  up  from  the  cut  surface.  About  dilated  bronchi  there  is  in 
places  dull  red  or  grayish  red  consolidation  forming  an  encircling  zone. 
Situated  below  the  pleural  surface  within  an  area  of  consolidation  at  tin- 
posterior  border  of  the  left  lower  lobe  there  is  a  spot  3  em.  across  where 
the  tissue  is  yellow  and  has  in  places  undergone  purulent  softening.  Sev- 
eral smaller   abscesses   occur  nearby. 

Cultures  from  the  blood  of  the  heart  and  from  the  edematous  medias- 
tinum contain  hemolytic  streptococci.  From  the  abscess  are  grown  S. 
albus,  Pneumococcus  II  and  B.  influenzas.  The  purulent  contents  of  a  small 
bronchus  contains  S.  hcmolyticus,  B.  influenzas,  S.  aurens  and  a  few  pneumo- 
cocci. 

Microscopic  examination  shows  that  the  epithelium  of  dilated  bronchi 
has  disappeared  and  the  denuded  surface  is  covered  by  fibrin  and  polynuclear 
leucocytes;  fissures  extend  from  the  lumen  through  the  bronchial  wall  into 
the  surrounding  alveolar  tissue.  A  zone  of  fibrinous  pneumonia  surrounds 
these  bronchi  and  fissures  in  the  bronchial  wall  penetrate  into  this  zone. 
One  dilated  bronchus  2.-I  mm.  in  diameter  with  no  cartilage  in  its  wall 
has  vascular  connective  tissue  covered  by  epithelium  on  one  side,  whereas 
the  remainder  of  the  circumference  is  formed  by  exposed  alveoli  filled  with 
fibrin,  the  bronchial  wall  having  disappeared.  A  section  through  a  part 
of  the  abscess  which  has  been  mentioned  shows  a  very  irregularly  formed 
cavity  approximately  1  x  0.7  cm.  Remains  of  bronchial  wall,  consisting" 
of  very  vascular  tissue  covered  hy  flat  epithelium  in  several  layers,  indicate 
the  origin  of  the  cavity.  Between  these  remnants  of  bronchi  deep  pockets 
extend  into  the  pulmonary  tissue  which  in  the  margin  of  the  cavity  is  the 
site  of  fibrinous  pneumonia.  In  one  place,  in  contact  with  the  cavity,  a 
wide  area  of  consolidated  tissue  has  undergone  necrosis  and  both  alveolar 
walls  and  their  contents  have  lost  their  nuclei.  Leucocytes  which  are 
accumulating  at  the  margin  of  the  necrotic  patch  form  a  line  of  demarca- 
tion between  living  and  dead  tissue. 

Abscess  may  be  the  result  of  the  profound  changes  which 
occur  in  the  bronchi  as  the  result  of  influenza.  Necrosis 
caused  by  bacteria  within  the  bronchi  weakens  and  in 
places  destroys  the  wall.  Bacteria  penetrate  into  the  sur- 
rounding tissue  and  hemolytic  streptococci  (or  staphylo- 
cocci) may  produce  localized  abscesses.  These  abscess- 
are  usually  situated  near  the  pleural  surface  of  the  lung,  be- 
cause destructive  changes  causing  rupture  of  the  bronchial 


208      PNEUMONIAS  AM*   INFECTIONS  OF   RESPIRATORY   TRACT 

wall  occur  more  frequently  in  the  smaller  peripheral  bron- 
chi than  in  the  larger  bronchi  containing  cartilage.  Al>- 
-  ;esses  occur  more  frequently  at  the  liases  of  the  lungs, 
because  the  mosl  severe  changes  in  the  bronchi  occur  in 
the  dependent  part.     (See  "Bronchiectasis,"  p.  240.) 

Healing-  of  Abscess. — The  following  autopsy  is  of  interest 
in  relation  to  the  treatment  of  pulmonary  abscess  and  as- 
sociated empyema. 

Autopsy  467. — P.  ('..  white,  aged  twenty-five,  a  farmer  from  Missouri, 
had  been  in  military  service  three  months.  Illness  began  September  27, 
thirty  days  before  death,  and  the  patient  was  admitted  the  day  following 
onsel  with  headache,  backache  and  cough.  Pneumonia  with  consolidation 
in  the  right  lower  lobe  was  recognized  on  the  sixth  day  of  illness.  On  the 
ninth  day  500  c.c.  of  fluid  were  withdrawn  from  the  righl  pleural  cavity; 
there  were  cyanosis  and  dyspnea.  On  the  eleventh  day  700  c.c.  of  fluid 
were  withdrawn.  On  the  twelfth  day  thoracotomy  was  performed  and  100 
c.c.  of  greenish  fluid  were  removed.  The  patienl  V  condition  improved  for 
a  time,  but  on  the  twenty-sixth  day  1,000  c.c.  of  straw  colored  fluid  were 
aspirated  from  the  left  pleural  cavity  and  on  the  twenty-eighth  day  the 
same    amount    of    seropurulent    fluid    was    withdrawn. 

Anatomic  Diagnosis. — Healing  abscess  of  righl  lower  lobe  communicating 
with  the  pleural  cavity;  acute  purulent  pleurisy  with  closed  thoracotomy 
wound  cm  the  right  side;  purulenl  pleurisy  cm  tie'  left  side;  acute  broncho- 
pneumonia with  lobular  consolidation  in  the  left  lung;  purulent  bronchitis; 
bronchiectasis  with  formation  of  spherical  bronchiectatic  cavities;  acute 
splenic  tumor. 

A i  tin'  base  of  the  right  ehesl  is  a  (dosed  thoracotomy  wound  2  cm. 
in  length;  the  rigid  pleural  cavity  contains  200  c.c.  of  thick  creamy  pus 
and  the  cavity  is  lined  by  a  thick  tough  membrane.  The  left  pleural  cav- 
ity contains  son  e.C.  of  white  purulent  fluid  thinner  than  that  on  the  right 
side.  The  right  lung  is  compressed  into  the  posterior  and  inner  part  of 
the  chest.  The  upper  lobe  is  pink  and  air  containing:  the  posterior  and 
lower  part  of  the  lower  lobe  is  red  and  atelectatic,  and  fibrous  septa  are 
more  conspicuous  than  elsewhere.  The  pleura  of  the  external  surface  near 
the  basal  edge,  in  an  area  -  cm.  across,  is  depressed  and  yellowish  gray  in 
color.  In  the  center  of  this  area  is  a  small  opening  communicating  with 
a    pocket   0.5  cm.  across  within   the   substance  of  the  lung. 

In  the  lower  lobe  beneath  the  interlobular  surface  are  two  spherical 
bronchiectatic  cavities,  each  about  1.5  cm.  across,  with  smooth  lining  in 
continuity  with   two  branches  of  the  same  bronchus  of  medium  size. 

Bacteriologic  examination  showed  the  presence  id'  S.  hemolyticus  in  the 

blood   of  the   heart.     No   growth   was   obtai 1    from    the   left    lung;    the    hit 

pleural  cavity  contained  hemolytic  streptococci  and  S.  aureus,  the  laltcr  in 


PATHOLOGY  AND  BACTEBIOLOGY    FOLLOWING    I X  I'M   lOX/A     201) 

small    number.     S.   hemolyticus   and    B.   influenzas   were   grown    from   the   Lefl 
main  bronchus. 

A  microscopic  section  through  the  abscess  and  its  communication  with 
the  pleura  shows  that  its  cavity  contains  polynuelear  leucocytes  and  the 
wall  is  formed  by  granulation  tissue  covered  by  fibrin.  Some  alveoli  out- 
side the  abscess  contain  compact  balls  of  fibrin  containing  a  few  fibroblai  I  : 
this  fibrin  stains  deeply  with  hematoxylin  as  if  it  contained  calcium.  The 
surface  of  the  lung  is  covered  by  fibrin   in   process  of  organization. 

In  the  foregoing  instance  a  pulmonary  abscess  on  the 
right  side  lias  ruptured  into  the  pleura  and,  completely 
separated  from  the  adjacent  lung  by  a  wall  of  newly  formed 
tissue,  is  in  process  of  healing.  It  shows  that  these  pul- 
monary abscesses  below  the  pleura  may  heal  provided 
drainage  is  established  by  rupture  into  the  pleural  cavity 
and  subsequent  evacuation  of  pleural  exudate.  It  is  note- 
worthy that  in  this  instance  empyema  extended  from  the 
right  to  the  left  pleural  cavity,  both  S.  hemolyticus  and  S. 
aureus  were  found  at  autopsy.  The  thoracotomy  wound 
on  the  right  side  was  closed  at  autopsy. 

Interstitial  Suppurative  Pneumonia 

A  second  type  of  suppurative  pneumonia  is  characterized 
by  acute  inflammation  of  interstitial  tissue  between  the  sec- 
ondary lobules  of  the  lung  and  by  acute  lymphangitis ;  sup- 
puration involves  the  interstitial  septa  and  the  walls  of  the 
lymphatics.  The  lesion  is  designated  by  Kaufmann,1 
Beitzke2  and  others  acute  interstitial  pneumonia.  Pneu- 
monia dissecans  in  which  solution  of  interstitial  tissue  iso- 
lates sections  of  lung  tissue  is  said  to  be  a  consequence  of 
the  lesion.  Many  text  books  of  pathology,  overlooking 
the  occurrence  of  this  lesion,  limit  the  consideration  of  in- 
terstitial pneumonia  to  chronic  processes  in  which  the  in- 
terlobular and  interalveolar  fibrous  tissue  is  increased. 

Acute  inflammation  and  edema  of  the  interlobular  septa 
of  the  lung  with  no  suppuration  is  often  found  with  both 
lobar  and  bronchopneumonia  and  is  occasionally  so  far  ad- 

1Kaufmann:      Snezielle   PaHiologisclie  Anatomic    1909,    ed.    5.   p.    260. 

2Beitzke:     Respirations   Organe.     Aschoff's   Path.   Anat.,    1913   ed.    3,    Vol.   II,   p.   SOS. 


I'll)      PNEUMONIAS  AND   [NFECTTONS  OF   RESPIRATOR'S   TRACT 

vanced  that  it  can  be  recognized  on  gross  examination  of 
the  lungs.  In  a  small  area  interlobular  septa  are  conspicu- 
ous as  yellowish  lines  of  edematous  appearance  which  may 
be  1  to  1.5  mm.  in  thickness  and  sometimes  form  a  network 
with  rectangular  or  polygonal  meshes.  The  gelatinous  ap- 
pearance of  the  edematous  fibrous  tissue  does  no1  suggest 
suppuration.  Microscopic  examination  shows  that  the 
tissue  is  distended  by  edema  and  contains  fibrin  and  poly- 
nuclear  leucocytes;  the  lymphatics  are  distended  and  con- 
tain a  network  of  fibrin  within  which  leucocytes  are  nu- 
merous. Inflammatory  edema  of  the  interstitial  tissue  has 
been  recognized  at  autopsy  four  times  in  association  with 
bronchopneumonia  (Autopsy  253  with  Pneumococcus  II; 
Autopsy  335,  with  Pneumococcus  TV  and  S.  viridans;  Au- 
topsy 477  with  S.  hemolyticus  and  Autopsy  498  with  S. 
viridans);  twice  with  lobar  pneumonia  (Autopsy  343  with 
Pneumococcus  IV  and  Autopsy  353  with  atypical  Pneu- 
mococcus II) ;  twice  with  combined  lobar  and  broncopneu- 
monia  (Autopsy  273  with  S.  hemolyticus  and  Pneumococcus 
IV  and  Autopsy  357  with  Pneumococcus  IV).  Edema  of 
interstitial  septa  was  recognized  at  autopsy  in  the  imme- 
diate neighborhood  of  an  abscess  three  times  (Autopsies 
277  and  27S  with  hemolytic  streptococci  and  Autopsy  282 
with  hemolytic  streptococci  and  Pneumococcus  II).  In 
these  instances  of  inflammation  and  edema  the  lymphatics 
are  found  distended  by  fibrinous  thrombi,  and  it  is  probable 
that  occlusion  of  lymphatics  determines  the  occurrence  of 
inflammatory  edema  within  the  surrounding  tissue.  In- 
flammation has  not  proceeded  to  suppuration. 

AVith  interstitial  suppurative  pneumonia,  interlobular 
connective  tissue  is  marked  by  conspicuous  yellow  lines, 
1  to  3  or  even  5  mm.  in  thickness,  forming  a  network  with 
polygonal  meshes  which  represent  secondary  lobules  (Figs. 
10  and  11).  The  distended  septa  not  infrequently  have 
bead-like  enlargements  at  intervals  and  Prom  the  cut  sur- 
face it  is  often  possible  to  scrape  away  creamy  yellow  pus. 


PATHOLOGY  AND  BACTERIOLOGY  FOLLOWING 


INFLUENZA     211 


l^s^^ssss^essis  asrs-a-  s**-^ 


212      PNEUMONIAS   AND   [NFECTIONS  OF   RESPIRATOR'S   TRACT 


Fig  11.— Suppurative  int.rsii.ial  pneumonia;  the  left  lower  lobe  is  the  site  of  almost 
uniform  consolidation  and  here  interstitial  septa  and  their  lymphatics  arc  distended  with 
pus       |  is    more   extensive    interstitial    suppuration    in    the   upper   lobe  where    consoi- 

t.     The   cloudy   appearance   of   the   consolidated   lung   is  well   shown.     Au 
topsy   452. 


PATHOLOGY  AND   BACTERIOLOGY    FOLLOWING    INFLUENZA     213 

These  linos  of  suppuration  invariably  extend  up  to  the 
pleura  and  are  often  broadest  immediately  below  it.  Adja- 
cent septa  which  have  not  undergone  suppuration  are  much 
thickened  and  have  the  yellowish  gray  appearance  produced 
by  edema. 

Suppurative  interstitial  pneumonia  frequently  occurs  in 
association  with  bronchopneumonia  consolidation  which 
may  be  peribronchiolar,  hemorrhagic  or  lobular,  but  there 
is  in  addition  consolidation  of  the  pulmonary  tissue  between 
the  inflamed  septa  which  may  affect  part  of  a  lobe,  an  en- 
tire lobe,  or  parts  of  several  lobes;  it  does  not  exhibit  the 
characters  of  confluent  lobular  pneumonia. 

In  approximately  half  of  the  cases  consolidation,  asso- 
ciated with  interstitial  suppuration,  has  been  lobar  in  dis- 
tribution (Fig.  11).  The  tissue  is  laxly  consolidated,  finely 
granular,  and  has  a  cloudy  red  or  gray  appearance.  The 
coarsely  granular  surface  of  lobar  pneumonia  is  absent. 
The  affected  lung  may  weigh  1,500  or  1,650  grams.  Oc- 
casionally, interstitial  septa  of  air  containing  lung  tissue 
is  the  site  of  suppurative  inflammation  or  edema.  In 
Autopsy  452  the  lower  lobe,  save  a  small  part  at  the  base, 
is  laxly  consolidated;  interstitial  septa  in  the  consolidated 
area  are  yellow,  1.5  to  2  mm.  in  thickness,  beaded  and  ex- 
ude purulent  fluid  on  pressure.  In  the  adjacent  part  of 
the  upper  lobe  there  is  a  patch  of  consolidation,  and  a  net- 
work of  yellow  thickened  septa  extends  from  it  far  into  the 
surrounding  air  containing  tissue.  The  weight  of  the  right 
lung  is  635  grams;  of  the  left,  1,650  grams. 

The  distribution  of  interstitial  suppuration  in  21  in- 
stances, including  4  in  which  the  lesion  has  occurred  in  the 
same  lungs  with  abscess  formation,  has  been  as  follows : 
right  upper  lobe,  9  instances ;  middle  lobe,  4 ;  lower  lobe.  5 : 
left  upper  lobe,  7 ;  left  lower  lobe,  6.  In  6  of  these  autop- 
sies more  than  one  lobe  of  the  same  lung  has  been  affected 
by  the  lesion ;  in  2  autopsies  parts  of  both  lungs  have  been 
affected.     Localized  abscess  of  the  lung  is  more  common  in 


214      PNEUMONIAS  ANI>   [NFECTIONS  OF   RESPIRATOR!    TRACT 

the  lower  than  in  the  upper  lobes,  bul  suppuration  of  the 
interstitial  tissue  is  more  often  found  in  the  upper  lobes. 

The  duration  of  illness  with  interstitial  suppurative 
pneumonia  lias  varied  from  six  days  to  five  weeks.  In  over 
half  of  the  cases  death  has  occurred  during  the  second  week 
of  illness. 

The  bacteriology  of  these  cases  is  shown  in  Table 
XLYIM. 

Tabli    XLVIII 


w 

m 
ft    u 

O     Eh 

v.    u 

PNEUMOCOCCl 

HEMOLYTIC 
STREPTOCCX  |   | 

STAPHYLO- 
COCCI 

B.   IXI'I.IKXZ.K 

■r. 

o   ? 
v.    - 

Eh     H 
g     & 

-    o 

Eh 
.      K 

o    ? 

Is   - 

z  E 

-    a 

£ 

Eh 
.      X 

o    ? 

X     - 

Eh      K 

o   s 

«    'k 
w    ? 

Eh 

v. 

3      = 

x    - 

.-    - 
v.    > 

-  - 

Bronchus 

10 

9 

90.0 

5 

50.0 

10 

100.0 

Lung 

20 

1 

5.0 

17 

85.0 

5 

25.0 

7 

35.0 

Blood 

21 

>) 

9.5 

17 

81.0 

S.  hemolyticus  lias  been  almost  invariably  present  in 
lungs,  heart's  blood  and  bronchi.  In  16  of  21  autopsies 
hemolytic  streptococci  have  been  obtained  from  the  blood 
in  pure  cultures,  in  one  instance  associated  with  pneumo- 
coccus.  With  associated  empyema,  pericarditis  or  peri- 
tonitis, the  same  microorganism  lias  been  found  in  the 
pleural  cavities,  pericardium  or  peritoneum.  Further- 
more, microscopic  examination  lias  demonstrated  the  pres- 
ence of  chains  of  streptococci  in  the  affected  interlobular 
tissue  and  in  much  greater  abundance  in  the  distended 
lymphatics. 

Nevertheless  in  2  instances  no  streptococci  have  been 
found.     These  cases  are  as  follows: 

Autopsy  330. — Illness  began  with  symptoms  of  influenza  ten  days  before 
death;  signs  of  pneumonia  were  recognized  three  days  before  death.  There 
is  firm,  gray  red  consolidation  of  the  entire  left  upper  lobe;  the  interlobular 
septa  are  here  indicated  by  yellow  lines  of  obvious  suppuration  and  thick  pus- 
like fluid  exudes  from  the  cut  surface  of  the  consolidated  tissue.  The  upper 
half  of  the  lefl  lower  lobe  has  undergone  gray  hepatization,  bul  here  there 
i-  no  distention  of  the  interlobular  septa.  There  is  fibrinopurulent  pleurisy 
on  the  left  side  with  accumulation  of  400  c.c.  of  fluid.     Pneumocoecus  IV   is 


PATHOLOGY  AND  BACTERIOLOGY   FOLLOWING    I  X  I'M  '  KXXA     215 

obtained  from  the  blood  of  the  heart  and  from  the  Lung.     In  the  suppurating 
tissue  diplococci  which  stain  by  Gram's  method  are  present  in  Large  number; 

there  are  a  few  short  chains. 

Autopsy  379. — Illness  began  seven  days  before  death  with  influenza; 
signs  of  pneumonia  were  first  recognized  the  day  before  death.  The  middle 
lobe  of  the  right  lung  is  firmly  consolidated;  on  section  there  is  mottling  of 
deep  red  and  pinkish  red  and  the  cut  surface  is  coarsely  granular.  The  inter- 
stitial septa  are  distended  by  fluid  and  are  grayish  yellow.  There  is  fibrino- 
purulent  pleurisy  on  the  right  side  with  .accumulation  of  600  C.C  of  fluid. 
Pneumocoecus  atypical  II  is  obtained  from  the  blood  of  the  heart.  A  large 
bacillus  unstained  by  Gram's  method  is  obtained  from  the  right  lung  and  from 
the  right  main  bronchus.  In  the  bronchus  are  a  few  influenza  bacilli.  In  the 
suppurating  and  necrotic  tissue  of  the  interstitial  septa  are  found  diplococci 
and  chains  of  i  to  6  cocci  in  great  number;  a  few  large  Gram-negative  bacilli 
are  found. 

In  both  these  autopsies  consolidation  had  the  characters 
of  lobar  pneumonia,  and  pneumococci  were  obtained  from 
the  blood  of  the  heart.  It  is  possible  that  streptococci  failed 
to  grow  or  while  present  elsewhere  were  absent  at  the  spot- 
where  cultures  were  made. 

It  is  noteworthy  that  B.  influenzae  was  found  in  the  bron- 
chi in  every  instance  (10)  in  which  cultures  were  made, 
but  was  obtained  much  less  frequently  from  the  lung.  In 
one  instance  (Autopsy  474)  this  microorganism  was  found 
in  the  blood  in  association  with  hemolytic  streptococci. 
There  was  suppurative  interstitial  pneumonia  in  the  left 
lung  and  abscess  in  the  right  lower  lobe  with  rupture  into 
the  cavity  and  empyema.  Hemolytic  streptococci  and  B. 
influenza?  were  found  in  the  bronchus,  right  rjleural  cavity 
and  blood  of  the  heart. 

In  4  instances  (Autopsies  251,  259,  295  and  474)  inter- 
stitial suppurative  pneumonia  has  been  associated  with 
abscess  formation.  In  one  instance  (Autopsy  251)  the 
right  middle  lobe  has  been  the  site  of  interstitial  suppura- 
tion and  abscess  formation;  in  another  (Autopsy  295)  the 
left  lower  lobe  has  been  the  site  of  both  lesions,  but  in  the 
other  2  instances  suppurative  interstitial  pneumonia  and 
abscess  formation  have  occurred  in  opposite  lungs.     In  all 


216      PNEUMONIAS  AXn   INFECTIONS  OF  RESPIRATOR'S   TRACT 

4  autopsies  hemolytic  streptococci  have  been  found  in  the 
blood  o!'  the  heart  and  in  Lungs  or  bronchi. 

Empyema  lias  been  present  in  all  bu1  3  of  _1  instances  of 
interstitial  suppurative  pneumonia. 

Histologic  examination  of  hums  with  interstitial  sup- 
puration shows  that  the  interlobular  septa  arc  distended  by 
serum  and  contain  a  conspicuous  network  of  fibrin.     Poly- 


Fi,~.    1-- — Suppurative    interstitial    pneumonia,    showing    an    immensely    dilated    lymphatic 
containing  purulent   exudate,  a  short   distance  below  the  pleura.     Autopsy  474. 


nuclear  leucocytes  are  present  in  varying  number,  and  at 

times  densely  in  lilt  rale  the  distended  tissue;  it  is  not  un- 
common to  find  a  zone  of  densely  crowded  polynuclear  leu- 
cocytes along-  each  edge  of  the  septum,  whereas  the  central 
part  contains  comparatively  few.  Occasionally,  there  is 
hemorrhage  into  the  distended  connective  tissue. 


PATHOLOGY  AND  BACTERIOLOGY    FOLLOWING    I  X  I'M  '  KX/A     1\  ( 

Within  the  distended  septa  occur  greatly  dilated  Lym- 
phatics filled  with  polynuclear  leucocytes  (Figs.  L2  and  L3). 
Thrombosis  of  the  distended  lymphatics  has  usually  oc- 
curred, and  a  conspicuous  network  of  fibrin  in  which  are 
polynuclear  leucocytes  plugs  the  lumen.  Streptococci  in 
chains  of  variable  length  are  found  in  the  inflamed  inter- 
stitial tissue,  but  are  present  in  far  greater  number  within 
the  distended  lymphatics. 


KKKMijSHKaflQ 


y<  . 


Fig.    13. — Suppurative   interstitial   pneumonia   showing  a   dilated   lymphatic.     Autopsy    42S 


Necrosis  of  the  cells  which  fill  the  lymphatics  occurs  in 
spots,  usualry  in  the  center  of  the  thrombus,  and  occasion- 
ally affects  the  entire  contents  of  the  lymphatic ;  polynu- 
clear leucocytes  have  lost  their  nuclei  or  in  some  the  nu- 
cleus has  undergone  fragmentation.  In  these  spots  the  net- 
work of  fibrin  has  disappeared.  Not  infrequently  the  wall 
of  the  lymphatic  in  a  small  sector  or  throughout  the  cir- 


218      PNEUMONIAS  AND   INFECTIONS  OF   RESPIRATOR!    TRACT 

cumference  has  undergone  necrosis,  and  spots  of  necrosis 
may  occur  in  the  interlobular  septa  distended  by  inflam- 
matory exudate.  Wherever  necrosis  has  occurred,  chains 
of  streptococci  are  present  in  immense  number. 

Accumulation  of  polynuclear  leucocytes,  necrosis  of  these 
cells,  solution  of  fibriD  at  first  in  the  centers  of  the  lym- 
phatic thrombus  and  later  throughout,  occasionally  with 
necrosis  of  the  wall  of  the  vessel,  result  in  the  formation 
of  an  abscess  at  the  site  of  the  distended  lymphatic.  These 
lymphatics,  dilated  by  purulenl  fluid,  may  have  a  diameter 
Prom  2  to  3  mm.  and  may  cause  considerable  compression 
and  collapse  of  immediately  adjacent  alveoli.  Lymphan- 
gitis, distention  of  lymphatics,  thrombosis  and  finally  sup- 
puration may  occur  in  the  lymphatic  vessels  encircling  the 
blood  vessels  and  in  those  situated  in  the  adventitia  of  the 
bronchi  of  medium  size. 

The  alveoli  adjacent  to  the  distended  septa  are  tilled  by 
inflammatory  products;  edema  is  almost  invariably  pres- 
ent and  the  alveoli  may  contain  serum  and  desquamated 
epithelial  cells;  fibrin  is  often  present,  hut  more  frequently 
polynuclear  leucocytes  are  predominant.  Not  infrequently, 
abscess  formation,  recognized  microscopically,  has  oc- 
curred in  contact  with  septa  most  often  immediately  below 
the  pleura.  Polynuclear  leucocytes  are  present  in  immense 
number  and  alveolar  septa  have  disappeared;  occasionally, 
with  abscess  formation  there  is  more  or  less  widespread 
necrosis  of  tissue,  cells  both  of  the  exudate  ami  of  the  alve- 
olar walls  having  lost  their  nuclei. 

Lymphatics  in  many  places  are  distended  and  plugged 
by  fibrinous  thrombi,  whereas  elsewhere  softening  of  the 
thrombus  has  been  brought  about  by  suppuration.  Sup- 
puration, both  within  the  lymphatic  and  in  adjacent  alve- 
oli, appears  to  he  secondary  to  lymphatic  obstruction.  In 
some  instances  the  lymphatic  appeal's  to  have  undergone 
distention  after  the  thrombus  has  formed,  for  between  the 


PATHOLOGY  AND  BACTERIOLOGY    FOLLOWING    INTLUEXZA     219 


thrombus  and  the  wall  of  the  lymphatic  a  channel  is  occa- 
sionally found  containing  uncoagulated  lymph. 

Acute  endophlebitis  has  been  repeatedly  observed  in  as- 
sociation with  interstitial  suppurative  pneumonia  (Fig. 
14).  The  lesion  usually  occurs  in  veins  situated  within  the 
septa  which  are  the  site  of  intensely  acute  inflammation 
associated  with  necrosis.  The  wall  of  the  vein  appears  to 
be  so  injured  by  the  surrounding  changes  that  polynuclear 


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S^^fejfLT:^ 


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il>*  I*-    •.-•''■ 


*  Vl"   -'•  •     v;i"'.    '..-.    ;»"""*  -v  i "oif"-  >'.-.  f'.  *"*'-*  'V    -,      »  '     -^.  Ww*** 


Fig.  14. — Endophlebitis  occurring  in  association  with  suppurative  pneumonia;  the 
intima  contains  lymphoid  cells  in  great  number;  at  one  spot  there  is  a  small  thrombus 
adherent  to  the  intima.     Autopsy  325. 

leucocytes  and  small  mononuclear  cells  accumulate  below 
the  endothelium.  Throughout  the  circumference  of  the 
veins,  often  0.5  to  1  mm.  in  diameter,  the  endothelium  is 
separated  from  the  underlying  media  by  polynuclear  leu- 
cocytes which  form  a  conspicuous  zone  encircling  the  lu- 
men. Some  cells  of  lymphoid  type  are  usually  present 
among  the  polynuclear  leucocytes.     Polynuclear  leucocytes 


220      PNEUMONIAS  AM'   INFECTIONS  OF   RESPIRATORY  TRACT 

are  often  adherenl  to  the  endothelial  lining  of  the  vessel 
and  are  do1  infrequently  fixed  in  the  process  of  passing 
through  tlif  endothelium.  The  lesion  may  be  more  severe 
(Autopsy  325),  so  thai  the  endothelium  lias  disappeared, 
and  upon  the  exposed  surface  fibrin  is  deposited;  within 
this  fibrin  polynuclear  leucocytes  are  numerous  and  nu- 
clear fragmentation  lias  occurred.  The  middle  coat  of  the 
vessel  usually  contains  few  cells:  some  polynuclear  leuco- 
cytes within  it  may  be  stretched  out  as  it'  in  process  of  wan- 
dering through  the  wall. 

Tn  other  instances  the  accumulation  of  cells  below  the 
endothelium  is  almost  wholly  mononuclear.  Cells  of  the 
type  of  lymphocytes  occur,  but  more  abundant  are  slightly 
larger  cells  with  more  abundant  cytoplasm.  These  cells 
may  form  a  thick  zone  below  the  intima  throughout  the  en- 
tire circumference  of  the  lesion.  It  seems  probable  that 
these  cells,  like  the  polynuclear  leucocytes,  are  derived  Prom 
circulating  blood  within  the  lumen  of  the  vessel,  for  small 
cells  of  the  type  of  lymphocytes  are  not  infrequently  found 
adherent  to  the  lumen  and  occasionally  one  is  fixed  in 
process  of  passing  through  the  endothelium. 

This  endophlebitis  appears  to  be  the  result  of  changes 
outside  the  vessel;  there  is  usually  necrosis  of  the  adjacent 
tissue  and  the  production  of  the  lesion  is  favored  by  lymph 
stasis:  as  the  result  of  injury  to  the  vessel  wall,  polynuclear 
leucocytes  in  response  to  chemotaxis,  or  with  milder  irrita- 
tion, mononuclear  cells,  wander  through  the  endothelium 
and  accumulate  below  it  perhaps  on  account  of  the  greater 
impermeability  of  the  middle  coal  to  the  passage  of  cells. 

The  lesion  described  does  not  occur  exclusively  with  in- 
terstitial suppurative  pneumonia  caused  by  hemolytic 
streptococci,  but  has  been  found  in  association  with  abscess 
formation  (Autopsies  354  and  383)  caused  by  hemolytic 
streptococci  or  (Autopsy  322)  caused  by  staphylococci. 
Tn  1  instance  it  has  been  found  with  lobar  pneumonia  (Au- 
topsy 320)  caused  by  atypical  Pneumococcus  II  and  in  2 


PATHOLOGY  AND  BACTETt I O I, OiiY    FOLLOWING    I  X  I'M  I  KN'ZA     22] 

instances  with  combined  lobar  and  bronchopneumonia 
(Autopsy  357  with  Pneumococcus  IV;  Autopsy  •!!)-!  with 
Pneumococcus  II).  In  these  3  instances  there  has  been  in- 
terstitial inflammation,  edema  and  lymphangitis  without 
suppuration. 

Interstitial  suppurative  pneumonia  of  long  standing  may 
occasionally  be  accompanied  by  chronic  changes  which 
bring  about  thickening  of  the  interlobular  tissue.  In  the 
following  autopsy  acute  suppurative  inflammation  in  the 
left  lung  has  been  associated  with  conspicuous  thickening 
of  interlobular  septa  in  the  right  lung. 

Autopsy  474. — I.  H.,  white,  aged  twenty-one,  was  a  native  of  Oklahoma 
and  had  been  in  military  service  one  month.  His  illness  began  with  influenza 
thirty-six  days  before  death;  he  was  admitted  to  the  base  hospital  thirty-one 
days  before  his  death  with  signs  of  pneumonic  consolidation  of  the  right 
lower  lobe.  Evidence  of  fluid  in  the  right  pleural  cavity  was  obtained  two 
weeks  before  death,  and  from  100  to  700  c.c.  of  thick  purulent  fluid  were  as- 
pirated on  five  occasions.  Hemolytic  streptococci  were  found  in  the  aspirated 
fluid. 

Anatomic  Diagnosis. — Interstitial  suppurative  pneumonia  in  left  lung; 
abscess  of  right  lower  lobe  with  rupture  into  pleural  cavity;  thickening  of 
interlobular  septa  of  right  lower  lobe ;  double  purulent  pleurisy  with  thorac- 
otomy on  right  side ;   serofibrinous  pericarditis. 

The  right  pleural  cavity  contains  85  c.c.  of  thick  purulent 
fluid;  the  right  lung  (Fig.  9)  is  collapsed  and  pushed  to  the 
median  line,  being  bound  by  firm  adhesions  to  the  pericar- 
dium. Over  the  external  and  basal  surfaces  is  a  localized 
cavity  walled  off  by  adhesions.  An  abscess  cavity  in  the 
lower  part  of  the  lower  lobe  communicates  through  a  per- 
foration in  the  basal  surface  of  the  lung  with  the  pleural 
cavity  and  is  in  free  communication  with  a  small  bronchus. 
About  the  abscess  the  lung  is  red  and  laxly  consolidated, 
but  elsewhere  air  containing ;  throughout  the  lower  half  of 
the  lower  lobe,  the  interlobular  septa  are  marked  by  con- 
spicuous yellowish  gray  lines  about  1  mm.  in  thickness. 
Between  these  thickened  septa  the  lung  tissue  contains  air. 
The  lung  weighs  600  grams.  The  left  lung  (Fig.  10)  is  vo- 
luminous and  heavy,  weighing  1,320  grams.     The  surface  is 


222      PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATOR'S   TRACT 

everywhere  covered  by  thickened  pleura  and  fibrin,  the 
pleural  cavity  containing  150  c.c.  of  thick  purulent  fluid. 
The  lung  is  consolidated  varying  in  color  from  a  fleshy  red 
to  yellowish  gray.  The  surface  is  very  conspicuously 
marked  by  yellow  lines  2  or  3  mm.  thick,  corresponding  to 
the  interlobular  septa  which  have  undergone  suppuration. 
The  septa  have  bead-like  swellings  along  their  course,  and 
when  pus  escapes  from  the  cut  surface  small  cavities  re- 
main at  the  site  of  these  swellings. 

Bacteriologic  examination  has  shown  hemolytic  strepto- 
cocci in  the  blood,  lefi  lung,  right  and  Lefi  pleural  cavities, 
and  right  bronchus.  B.  influenza1  has  been  found  in  the 
bronchus,  in  the  righl  pleura  and  in  the  heart's  blood.  A 
few  colonies  of  S.  aureus  have  been  found  on  the  plate 
from  the  right  pleural  cavity  (site  of  thoracotomy). 

Microscopic  examination  of  the  right  lower  lobe  shows 
that  the  interstitial  septa  are  much  thickened  by  young 
fibrous  tissue  infiltrated  with  lymphoid  and  a  few  plasma 
cells.  Large  mononuclear  cells  with  granular  cytoplasm  are 
very  numerous.  A  lymphatic  is  much  distended  and  con- 
tains a  few  polynuclear  leucocytes  and  many  lymphoid  and 
large  mononuclear  cells.  There  is  no  suppuration.  Sec- 
tions from  the  right  lung  show  suppurative  lymphangitis 
with  suppurative  inflammation  of  interstitial  tissue. 

The  right  lung  is  the  site  of  a  healing  lesion  of  the  inter- 
stitial tissue  which  has  developed  simultaneously  with 
acute  interstitial  suppurative  pneumonia  in  the  left  lung. 
Both  lesions  are  doubtless  caused  by  S.  hemolyticus.  This 
healing  lesion  exhibits  little  similarity  to  the  interstitial 
bronchopneumonia  described  by  several  observers  with 
both  measles  and  influenza. 

The  following  autopsy  furnishes  further  evidence  that 
interstitial  suppurative  pneumonia  exhibits  a  tendency  to 
heal.  Proliferation  of  endothelial  cells  lining  the  inflamed 
lymphatics  gives  rise  to  phagocytic  cells  which  aid  in  re- 
moving the  accumulated  leucocytes. 


PATHOLOGY  AND   BACTERIOLOGY    FOLLOWING    [NFLUENZA     223 

Autopsy  397. — N.  P.,  white,  aged  twenty-one,  farmer,  a  native  of  Okla- 
homa, had  been  in  military  service  twenty-one  days.  Illness  began  twenty-two 
days  before  death,  the  patient  being  admitted  on  the  day  following  onset 
with  influenza,  pharyngitis  and  bronchitis.  A  diagnosis  of  lobar  pneumonia 
was  made  fourteen  days  before  death.  The  Lef1  pleural  cavity  was  aspirated 
twelve  days  later  and  800  c.c.  of  thick  yellow  pus  were  withdrawn.  Hemolytic 
streptococci  were  found  in   the   sputum    five  days   before   death. 

Anatomic  Diagnosis. — Interstitial  suppurative  pneumonia  in  lefl  upper 
lobe;  acute  bronchopneumonia  with  lobular  consolidation  in  righl  upper  lobe; 
localized  purulent  pleurisy  ou  left  side  with  compression  and  atelectasis  of 
left  lung;  compensatory  emphysema  of  right  lung;  purulent  bronchitis;  be- 
ginning serofibrinous  pericarditis;  chronic  passive  congestion  of  liver,  spleen 
and  kidneys. 

The  right  lung  is  very  voluminous,  free  from  coal  pigment  and  bright 
pink  save  over  lobular  patches  of  consolidation  -which  have  a  bluish  red  color; 
the  bronchi  contain  mucopurulent  material.  The  anterior  surface  of  the  left 
lung  is  bound  to  the  chest  wall  by  firm  adhesions,  but  over  the  external  and 
posterior  surfaces  of  the  lung  there  is  a  localized  cavity  containing  1,100  c.c. 
of  turbid  fluid.  The  left  lung  is  collapsed  and  airless  with  deep  fleshy  red 
color.  In  the  upper  lobe  there  are  scattered  patches  of  consolidation  1.5  to 
2.5  cm.  across  where  the  tissue  is  grayish  red  and  coarsely  granular.  In  the 
adjacent  tissue  interstitial  septa  are  thickened  to  1  or  2  mm.  and  are  con- 
spicuous as  gray  bands.  Along  their  course  occur  bead-like  swellings  from 
which  purulent  fluid  can  be  scraped.  These  septa  at  one  point  reach  the 
anterior  surface  of  the  lung  where  the  pleural  cavity  is  in  large  part  obliter- 
ated by  adhesions;  here  there  is  an  encapsulated  pocket  4  x  1.5  em.  con- 
taining thick  creamy  pus. 

Bacteriologic  examination  of  the  blood  shows  the  presence  of  hemolytic 
streptococci;  cultures  from  the  lungs  contain  hemolytic  streptococci  and  B. 
influenza?. 

Microscopic  examination  shows  that  interlobular  septa  are  thickened  and 
infiltrated  with  plasma  cells  in  large  number.  Leucocytes  in  the  center  of 
much  dilated  lymphatics  have  undergone  necrosis  and  have  lost  their  nuclear 
stain.  About  the  periphery  of  the  lumen  and  evidently  derived  from  the 
swollen  endothelial  cells  which  surround  it,  are  numerous  large  mononuclear 
cells.  They  act  as  phagocytes  and  ingest  polynuclear  leucocytes.  Multinu- 
cleated giant  cells,  derived  from  these  cells,  occur.  In  several  places  throm- 
bosed lymphatics  in  process  of  organization  occur ;  the  lumen  is  filled  with 
compact  fibrin  which  is  invaded  by  fibroblasts  and  newly  formed  capillaries. 

The  process  just  described  is  analogous  to  that  which  oc- 
curs whenever  an  unopened  abscess  heals;  mononuclear 
cells  accumulate  and  act  as  phagocytes  ingesting  polynu- 
clear leucocytes. 


224      PNEUMONIAS  AND   INFECTIONS  OE   RESPIRATORS   TRACT 

The  following  instance  of  streptococcus  empyema  is  note- 
worthy because  no  suppurative  pneumonia  has  been  found 
in  association  with  it.  Nevertheless  the  character  of  the 
changes  present  in  the  lung  indicate  that  the  organ  has 
been  the  site  of  an  interlobular  inflammation  which  has 
healed. 

Autopsy  499. — J.  II.  M.,  white,  aged  twenty  Pour,  a  farmer  from  Arkan- 
sas, had  been  in  military  service  five  months.  Onsel  of  illness  began  two 
weeks  before  his  admission  to  the  hospital  on  November  15  with  cough,  fever, 
headache  and  malaise;  on  admission  there  was  acute  bronchitis.  Thirteen 
days  after  admission  the  patient  developed  parotitis  (mumps?);  five  days 
later  and  five  days  before  death  pleurisy  \v:is  recognized  on  the  right  side 
and  pneumonia  was  suspected.  Death  occurred  thirty-six  days  after  onset. 
The  temperature  on  admission  was  103.2  F.  and  remained  elevated  during 
cue  week  falling  by  lysis;  from  tins  time  until  the  pleurisy  was  recognized 
it  w;is  normal  and  later  it  remained  approximately  103°  F. 

Anatomic  Diagnosis. — Fibrinopurulent  pleurisy  on  right  side;  fibrinous 
pleurisy  on  left  side;  fibrinopurulenl  pericarditis;  chronic  interstitial  (inter- 
lobular) pneumonia  in  process  of  healing;  purulent  bronchitis;  acute  splenic 
tumor;   parenchymatous  degeneration  of  kidneys. 

The  right  pleural  cavity  contains  1,650  c.c.  of  grayish  yellow  fluid  con- 
taining an  abundant  sediment  of  softened  fibrin.  Part  of  this  fluid,  inure 
opaque  than  the  remainder  is  confined  in  a  localized  pockel  between  the  inner 
surface  of  the  lung  and  the  pericardium.  The  apex  and  anterior  surface 
of  the  right  upper  lobe,  over  an  area  about  7  cm.  across,  is  held  by  fibrinous 
adhesions  to  the  chest  wall;  when  this  adhesion  is  broken  a  pocket  is  exposed 
6.5  x  2.5  cm.  containing  fibrin  and  fluid.  The  pericardial  cavity  is  distended 
by  -"'.lO  c.c.  of  turbid  yellow  seropurulent  fluid.  The  pericardial  surfaces  are 
covered   by  shaggy,   tough  gray  fibrin. 

The  right  lung  is  collapsed;  the  lower  and  posterior  part  of  the  upper 
lobe  is  deep  red  and  atelectatic.  Throughout  the  upper  lobe  the  interlobular 
septa  are  thickened,  often  1  mm.  across  and  very  conspicuous;  in  the  lower 
i  in  1  anterior  tip  of  the  lobe  is  an  area  where  tissue  is  firm  grayish  red  and 
heavier  than  water.  The  lower  and  posterior  half  of  the  righl  lower  lobe 
is  firm  and  airless,  and  the  tissue  is  reddish  gray  or  gray  and  in  places  finely 
granulaT  on  section;  interlobular  septa  are  conspicuous.  Although  the  lung 
is  cut  into  thin  sections,  no  abscesses  are  found.  Bronchi  throughout  the  lung 
<  ontain  mucopurulent  fluid. 

The  left  lung  over  its  lower  half  is  covered  by  a  thin  layer  of  fibrin.  The 
tissue  is  crepitant  throughout  and  moderately  edematous.  Bronchi  contain 
mucopurulent  fluid. 

Hemolytic  streptococci  in  pure  culture  are  obtained  from  the  blood  of 
the  heart,  right  pleural  cavity  and  pericardium.  No  growth  is  obtained 
on  a  plate  inoculated  with  material  from  the  right  lower  lobe.  The  right 
bronchus  contains  hemolytic  streptococci  and  15.  influenza;. 


PATHOLOGY  AND  BACTERIOLOGY  FOLLOWING  INFLUENZA      225 

The  pleural  surface  of  the  right  lung  is  covered  by  a  thick  layer  of  fibrin 
which  has  undergone  advanced  organization.  Fibrous  sepia  within  the  lung 
are  much  thickened  by  the  presence  of  newly  formed  fibrous  tissue;  the  in 
terstices  of  the  tissue  are  distended  and  contain  fibrin  into  which  fibroblasts 
and  new  blood  vessels  have  penetrated.  Home  lymphatics  are  plugged  with 
fibrin  and  contain  polynuclear  leucocytes,  lymphoid  and  large  mononuclear 
cells.  In  several  places  organization  of  these  thrombi  is  beginning.  About 
the  blood  vessels  are  thrombosed  lymphatics  in  which  polynuclear  leucocytes 
and  mononuclear  cells,  are  equally  abundant.  Alveoli  immediately  adjacent 
to  blood  vessels  and  to  fibrous  septa  often  contain  fibrin,  and  alveoli  elsewhere 
contain  desquamated  cells  in  abundance. 

Ill  association  with  hemolytic  streptococci  in  the  blood, 
pleura  and  pericardium,  there  has  been  inflammation  of  the 
interlobular  septa  of  the  lungs  with  acute  lymphangitis; 
there  has  been  no  suppuration  and  the  lesion  is  in  process 
of  healing  with  new  formation  of  fibrous  tissue.  It  is  evi- 
dent that  this  lesion,  as  well  as  pleurisy  with  advanced  or- 
ganization, preceded  the  exacerbation  of  the  patient's  ill- 
ness which  occurred  five  days  before  death.  The  advanced 
chronic  changes  found  at  autopsy  indicate  that  the  pul- 
monary and  pleural  lesions  had  their  origin  during  the 
illness  which  was  present  at  the  time  of  admission  to  the 
hospital.  Interstitial  pneumonia  caused  by  hemolytic 
streptococci  was  of  mild  character  and  did  not  produce 
suppuration  within  the  lung ;  nevertheless,  hemolytic  strep- 
tococci which  reached  the  pleura  caused  empyema. 

Suppurative  Pneumonia  with  Multiple  Clustered  Abscesses 
Caused  by  Staphylococci 

In  the  preliminary  report  of  this  commission  published 
in  The  Journal  of  the  American  Medical  Association,  loc. 
cit.,  pg.  Ill,  we  described  suppurative  pneumonia  with  mul- 
tiple abscesses  caused  by  staphylococci  and  cited  4  instances 
of  the  lesion  which  followed  influenza.  Chickering  and 
Park4  published  in  a  subsequent  number  of  the  same  journal 

■•Chickering,  H.  T.  and  Park,  J.  II. :     Staphylococcus  Aureus  Pneumonia,   Tour.  Am.   Med. 
Assn.    1919,   lxxii,   617. 


_L(>      PNEUMONIAS  AND   INFECTIONS  OF   RESPIRATOR!    TRACT 

an  account  of  staphylococcus  pneumonia,  a  lesion  which  has 
heretofore  attracted  very  little  attention. 

In  a  small  group  <>f  cases  abscesses  in  the  hums  have  had 
characters  which  serve  to  distinguish  them  Prom  the  ab- 
scesses previously  described.  Small,  sharply  circumscribed 
yellow  nodules,  which  in  t heii- centers  have  undergone  sup- 
purative softening,  form  a  cluster  upon  a  red,  airless  back- 
ground (Figs.  15  and  Ki).  One  or  more  of  these  groups 
several  centimeters  across,  occur  in  the  lungs.  11  is  usually 
evident  that  the  abscesses  are  clustered  about  a  medium- 
sized  bronchus,  but  occasionally  with  increase  in  the  size 
of  the  small  cavities  the  lung  tissue  assumes  a  honey-combed 
appearance. 

These  clustered  abscesses  occur  in  association  with  bron- 
chopneumonia and  have  been  in  all  instances  associated 
with  purulent  bronchitis.  The  mucosa  of  the  small  bronchi 
may  be  destroyed  so  that  the  surface  is  eroded.  These 
small  clustered  abscesses  are  seen  as  conspicuous  yellow 
spots  immediately  below  the  pleura,  but  there  lias  been  no 
associated  empyema.  In  2  instances  these  abscesses  were 
accompanied  by  fibrinous  pleurisy,  but  in  the  remaining  au- 
topsies the  pleura  has  been  normal.  The  infrequency  of 
empyema  is  in  contrast  with  its  almost  invariable  presence 
when  a  streptococcus  abscess  is  found  below  the  pleura. 

Autopsy  280. — Onset  of  illness  with  malaise,  headache,  cough  and  fever 
was  on  September  24,  eight  days  before  death.  At  autopsy  there  were  hem- 
orrhagic peribronchiolar  rind  lobular  bronchopneumonia,  clustered  foci  of  sup- 
puration  in  right  lung,  purulent  bronchitis  and  fibrinous  pleurisy,  Hemo- 
lytic  streptococci  were  obtained  from  the  consolidated  lung  .and  from  a 
bronchus.  A  culture  from  the  right  lung  was  contaminated.  In  the  bronchus 
were  found  B.  influenza'  and  a  few  staphylococci.  Microscopic  examination 
of  the  abscesses  shows  thai  they  contain  Gram-staining  cocci  grouped  into 
staphylococcus  like  colonies. 

Autopsy  286. — Duration  of  illness,  which  began  September  l'.~  with 
symptoms  of  influenza,  was  nine  days.  At  autopsy  there  were  lobular  ami 
cunfliiriit  patches  of  bronchopneumonia,  clustered  abscesses  in  the  right  lung 
below  tlic  pleura,  purulent  bronchitis,  ami  serofibrinous  pleurisy  localized 
in  the  neighborhood  of  the  abscesses.  PneUmococcus  IV  was  obtained  from 
the  blood  of  the  heart,  and  Pneumococcus  IV,  staphylococci  and  P..  influenza' 
from  the   right   main  bronchus;    growth   failed  to   occur  on   plates  from  right 


PATHOLOGY  AND  BACTERIOLOGY    FOLLOWING    INFLUENZA     227 


Fig.   15. — Abscesses  in  two  clusters  caused  by  S.  aureus  in  upper  part  of  right  upper  lobe; 
confluent  lobular  consolidation  in  lower  part  of  lobe.     Autopsy  333. 


228      PNEUMONIAS  AXli   INFECTIONS  OF  RESPIRATOR'S  TRACT 

and  left  lungs.  Microscopic  examination  shows  the  presence  of  clumps  of 
cocci  with  staphylococcus  grouping  in  the  centers  of  the  small  abscesses. 
Section  through  one  abscess  shows  its  continuity  with  the  wall  of  a  bronchus j 
along  one  side  of  the  abscess  is  epithelium  composed  of  flattened  epithelial 
cells  in  multiple  layers  continuous  with  thai  of  the  bronchus;  the  remainder 
of  the   abscess   wall   is   formed    by   disintegrated   lung  tissue. 

Autopsy  322. — The  patient  was  admitted  with  influenza  eight  days  be- 
fore death;  signs  of  pneumonia  appeared  two  'lays  later,  and  on  the  follow- 
ing  day    Pneumococcus   IV    was   obtained    from   the    sputum.     At    autopsy 


1 

•"—■■-          -«-_ 

1  e 

Xg                    ""^BHe 

■ 

W  k    j£jf                                      ^^H 

fc^*)re^*8       ■ 

~JL 

#t| 

ll/la 

\ 

4  ■            \ 

: 

^   '' (*                       \ 

■    ■  - 

Fig.   16. — Abscesses  in  cluster  caused  by   S.  aureus  at   apex   of   right  upper   lobe.     Autopsy 

322. 


there  were  bronchopneumonia  with  lobar  consolidation,  abscesses  clustered 
aboul  a  bronchus  in  the  right  upper  lobe  and  purulent  bronchitis.  The 
blood  was  sterile;  S.  aureus  was  obtained  from  the  consolidated  part  of 
the  left  lung;  S.  aureus  and  Pneumococcus  III  from  the  abscesses  of  the  right 
lung.  Microscopic  examination  of  sections  of  abscesses  showed  the  pres- 
ence of  Gram-staining  cocci  in  staphylococcus  like  colonies,  surrounded  by 
necrotic  material  and  polynuclear  leucocytes;  Gram-negative  bacilli  re- 
sembling B.  influenzae  were  seen.     (See  Fig.  16.) 


PATHOLOGY  AND  BACTERIOLOGY    FOLLOWING    INFLUENZA     'I'li) 


Autopsy  333. — The  onset  of  influenza  was  fifteen  days  before  death;  a 
diagnosis  of  pneumonia  was  made  seven  days  before  death.  At;  autopsy  there 
were  confluent  bronchopneumonia,  clustered  abscesses  in  the  right  lung  and 
purulent  bronchitis  (no  pleurisy).  The  Mood  contained  Pneumococcus  II 
atypical.  S.  aureus  and  Pneumococcus  II  atypical  were  obtained  from  the 
abscesses;  S.  hemolyticus,  from  the  consolidated  left  lung;  8.  aureus,  B.  in- 
fluenzae and  a  few  hemolytic  streptococci,  from  the  bronchus.      (See   Fig.  15.) 

Autopsy  370. — The  patient  was  admitted  seventeen  days  before  death 
and  signs  of  pneumonia  were  noted  three  days  after  admission.  At  autopsy 
there  were  lobular  and  confluent  bronchopneumonia  and  small  abscesses  clus- 
tered about  bronchi  and  situated  within  the  gray  consolidated  lung;  purulent 
bronchitis  and  patches  of  atelectasis,  with  distention  of  the  lungs,  so  that  they 
failed  to  collapse  on  removal.  No  growth  was  obtained  from  the  heart 's 
blood;  S.  aureus  in  pure  culture  was  obtained  from  the  abscesses  of  the  right 
lung;  Si.  aureus,  Pneumococcus  IV  and  B.  influenzae  were  obtained  from  a 
small  bronchus  on  the  left  side. 

Autopsy  425. — Illness  began  with  influenza  twenty-nine  days  before 
death;  a  diagnosis  of  pneumonia  was  made  fourteen  days  before  death.  At 
autopsy  there  were  chronic  bronchopneumonia  with  tubercle-like  nodules  of 
consolidation  with  some  large  patches  of  consolidation,  multiple  small  ab- 
scesses giving  a  honey-combed  appearance  to  part  of  the  right  middle  lobe, 
purulent  bronchitis  and  bronchiectasis.  S.  hemolyticus  was  grown  from  the 
heart's  blood;  S.  hemolyticus,  B.  influenzae  and  S.  albus  from  the  lung.  Sec- 
tions of  an  abscess  contain  clumps  of  cocci.  An  abscess  cavity  has  along  one 
side  remains  of  a  bronchial  wall  covered  by  squamous  epithelium;  a  dilated 
bronchus,  cut  longitudinally,  terminates  in  this  irregular  abscess  cavity. 

Table  XLIX  shows  the  incidence  of  pneumococci, 
hemolytic  streptococci,  staphylococci  and  B.  influenzae  in 
the  foregoing  autopsies  with  abscesses  clustered  about 
bronchi : 

Table  XLIX 


w 

°     t 

PNEUMOCOCCI 

HEMOLYTIC 
STREPTOCOCCI 

STAPHYLO- 
COCCI 

B.  INFLUENZAE 

> 

°      ? 

E-i     H 
S     > 

w  a 

«    o 

> 

Eh      H 

m 

°    ? 

> 
°     ? 

PER  CENT 
POSITIVE 

Eronchus 

Lung 

Blood 

4 
6 
6 

2 
2 

2 

50.0 
33.3 
33.3 

2 
3 
2 

50.0 
50.0 
.33.3 

4 
4 

100.0 
66.7 

4 
2 

100. 
33.3 

Staphylococcus  shows  in  the  lung  the  same  tendency  to 
produce  localized  abscesses  which  it  exhibits  in  other  tis- 
sues of  the  body ;  it  invades  the  lung  by  way  of  the  bronchi. 


230      PNEUMONIAS  A.\l>   INFECTIONS  OF   RESPIRATOR'S   TRACT 

bu1  shows  no  ability  to  invade  lymphatics,  and  in  the  cases 
we  have  examined  rarely  enters  the  pleura  or  the  blood. 
In  all  of  these  cases  r>.  influenzae  has  been  Pound  in  the  bron- 
chi and  perhaps  precedes  the  staphylococcus  as  an  invader 
of  the  Lower  respiratory  passages.  Pneumococci  atypical 
1 1.  Types  III  and  I  V  liave  been  found  in  over  half  of  these 
cases.  The  significance  of  this  organism  is  emphasized  by 
the  2  cases  in  which  it  has  been  found  in  the  heart's  blood 
;it  autopsy.  It  appears  not  improbable  that  S.  aureus  has 
invaded  the  lung  already  the  site  of  bronchopneumonia 
caused  by  pneumococci. 

Notwithstanding  the  small  number  of  autopsies,  the  fig- 
ares  in  Table  X  LI  X.  showing  the  incidence  of  pneumococci, 
streptococci,  staphylococci  and  B.  influenza?,  arc  cited  so 
that  they  may  be  compared  with  the  corresponding  figures 
for  the  usual  type  of  streptococcus  abscess  (p.  203).  Tin1 
incidence  of  hemolytic  streptococci  is  relatively  low, 
whereas  that  of  staphylococci  approximates  100  per  cent. 
S.  aureus  was  present  in  great  number  in  the  lung  of  Au- 
topsies 322  and  333  and  in  pure  culture  in  the  abscess  of 
Autopsy  370.  Microscopic  examination  of  sections  from 
the  abscesses  which  have  been  described,  demonstrated  the 
presence  of  Gram-staining  cocci  in  characteristic  staphylo- 
coccus-like  clumps  within  the  exudate  of  the  abscesses;  scat- 
tered chains  of  streptococci  were  not  found.  In  those  in- 
stances (Autopsies  2S0  and  286)  in  which  cultures  failed  to 
demonstrate  staphylococci,  microscopic  examination  dem- 
onstrated staphylocoecus-like  clumps  of  bacteria  within  the 
abscess  cavity.  Cultures  were  usually  made  from  the  con- 
solidated lung  near  the  abscess  where  the  pleural  surface 
could  be  seared,  rather  than  from  the  pus,  so  that  in  some 
instances  the  microorganism  has  doubtless  escaped  detec- 
tion although  present. 

In  association  with  the  multiple  abscesses  which  have 
been  described,  injury  to  the  bronchi  and  bronchopneu- 
monia have  been  invariably  present.     Purulent  bronchitis 


PATHOLOGY  AND  BACTUUIOLOG  Y    FOLLOWING    I  X  I'M  'ION/A     231 

has  boon  present  in  nil  instances  of  this  lesion;  in  2  in- 
stances there  has  been  dilatation  of  the  bronchi,  and  in  1 
instance  in  which  the  onset  of  influenza  was  twenty-nine 
days  before  death,  there  has  been  advanced  bronchiectasis. 
Microscopic  examination  shows  that  the  epithelium  of  the 
bronchi  is  partially  or  completely  destroyed  and  that  de- 
struction of  the  underlying'  tissue,  with  acute  suppurative 
inflammation,  penetrates  to  a  greater  or  less  depth  into  the 
wall.  When  the  epithelium  of  the  bronchus  is  wholly 
destroyed  and  the  lumen  is  filled  and  distended  with  poly- 
nuclear  leucocytes,  a  cross  section  of  the  tube  has  the  ap- 
pearance of  a  small  abscess ;  but  more  careful  examination 
often  shows  that  the  engorged  mucosa  is  still  intact. 
Occasionally,  a  network  of  fibrin  forms  a  layer  covering  the 
denuded  mucosa.  Disintegration  of  the  superficial  tissue 
may  extend  to  the  muscularis  or  through  it,  and  may  pene- 
trate the  wall  of  the  bronchus.  The  tissue  in  contact  with 
the  exposed  surface  contains  man}''  polynuclear  leucocytes 
and  blood  vessels  plugged  with  fibrinous  thrombi,  but 
deeper  in  the  tissue  lymphoid  and  plasma  cells  are  more 
numerous.  In  2  instances  (Autopsies  286  and  425)  favor- 
able sections  have  demonstrated  that  the  wall  of  an  abscess 
on  one  side  consists  of  the  remains  of  a  bronchus,  covered 
by  epithelium  composed  of  squamous  cells,  whereas  the 
remainder  of  the  wall,  here  very  irregular,  is  formed  by 
partially  destroyed  alveoli  plugged  with  fibrin.  The  sup- 
purative process  has  penetrated  the  wall  of  the  bronchus 
on  one  side  and  extended  into  the  surrounding  alveolar 
tissue.  In  other  instances,  abscess  cavities  occur  within 
the  alveolar  tissue  of  the  lung  and  their  relationship  to 
bronchi  is  not  evident.  In  the  mass  of  polynuclear  leuco- 
cytes which  rill  the  abscess  cavity,  are  clumps  of  staphy- 
lococci in  great  abundance,  usually  forming  characteristic 
colonies  which  are  conspicuous  with  the  low  power  of  the 
microscope. 


232      PNEUMONIAS  ANH   [NFECTIONS  OF   RESPIBATOR'S  TRACT 

Empyema,  Pericarditis  and  Peritonitis 

No  sharp  line  can  be  drawn  between  nonpurulent  and 
purulent  pleurisy.  A  diagnosis  of  empyema  lias  been 
made  when  the  fluid  in  the  chest  has  become  opaque  and 
fibrin  has  undergone  softening  or  solution.  The  lesion 
has  been  designated  seropurulenl  when  there  has  been 
abundanl  thin,  opaque,  gray  fluid.  Pleurisy  lias  been 
designated  flbrinopurulenl  when  the  cavity  lias  contained 
opaque  fluid  and  raided  soft  white  or  yellowish  fibrin  ad- 
herent to  the  chest  wall;  this  fibrin  is  evidently  in  process 
of  disintegration  and  there  may  be  numerous  shreds  and 
Hakes  of  fibrin  which  subside  to  the  bottom  of  the  fluid. 
The  amount  of  fluid  in  the  cavity  may  occasionally  exceed 
1,700  c.c :  that  in  both  pleural  cavities  may  exceed  2,500  c.c. 
The  lesion  has  been  designated  purulent  when  fibrin  has 
almost  wholly  disappeared  and  the  cavity  contains  thick 
yellowish  white  fluid.  In  4  of  5  instances  in  which  tho- 
racotomy had  been  performed,  empyema  has  assumed  this 
otherwise  uncommon  type. 

Some  inflammation  of  the  pleura  is  almost  constantly 
found  in  association  with  all  forms  of  pneumonia,  but  in 
many  instances  is  so  slight  that  it  has  no  noteworthy  sig- 
nificance. Table  L  shows  the  incidence  of  various  types  of 
pleurisy. 

Table  L 


SUPPURA- 

INTERSTI- 

LOBAR 

BRONCHO- 

TIVE    PNEU- 

TIAL    SUPPU- 

PNEUMONIA 

PNEUMONIA 

MONIA   WITH 

RATIVA. 

ABSCESS 

PNEUMONIA 

No. 

% 

No. 

% 

No. 

% 

No.   [      % 

Xo  pleurisy  noted 

30 

46.9 

44 

55 

1 

2.6 

1 

5.9 

Serous  pleurisy 

5 

7.8 

9 

11.2 

Fibrinous  pleurisy 

10 

l.-,.i; 

0 

6.2 

1 

2.6 

Serofibrinous   pleurisy 

12 

18.2 

14 

17.5 

3 

7.7 

Seropurulent    pleurisy 

9 

23.1 

1 

5.9 

Fibrinopurulent  pleurisy 

7 

10.9 

5 

6.2 

17 

43.6 

12 

70.6 

Puruleni    pleurisy 

3 

3.7 

8 

20.5 

3 

17.6 

Total 

64 

80 

39 

17 

PATHOLOGY  AND  BACTEKIOLOGY  FOLLOWING    I  \  I'M   K XX A     233 

Empyema  has  occurred,  on  the  one  hand,  in  12.4  per  cent 
of  instances  of  lobar  pneumonia  and  in  9.9  per  cent  of  in- 
stances of  bronchopneumonia  alone.  It  lias  occurred,  on 
the  other  hand,  in  87.2  per  cent  of  instances  of  suppura- 
tive pneumonia  with  abscess  formation  and  in  94.1  per  cenl 
instances  of  interstitial  suppurative  pneumonia.  These 
suppurative  lesions  are  caused  by  hemolytic  streptococci, 
and  when  cultures  are  made  from  the  pleural  exudate  this 
microorganism  is  isolated. 

Of  16  instances  in  which  empyema  has  occurred  in  asso- 
ciation with  lobar  pneumonia  or  bronchopneumonia  unac- 
companied by  suppuration  in  6  there  has  been  infection 
with  hemolytic  streptococci.  Empyema  has  occurred  in 
the  absence  of  hemolytic  streptococci  only  10  times. 

Empyema  Caused  by  Hemolytic  Streptococci. — When 
necrosis  preceding  abscess  formation  has  occurred  in  the 
lung,  streptococci  are  found  in  immense  numbers  in  the 
dead  tissue.  The  pleura  overlying  the  abscess  undergoes 
necrosis  and  occasionally  streptococci  are  particularly  nu- 
merous upon  the  pleural  surface  of  the  necrotic  tissue.  In 
Autopsy  376  a  membrane  thin  as  tissue  paper,  representing 
the  pleura,  separated  an  abscess  containing  thick  pus  from 
the  pleural  cavity  which  was  the  site  of  empyema.  The 
abscess  may  rupture  into  the  pleural  cavity  and  at  the  same 
time  may  be  in  free  communication  with  a  bronchus  (Au- 
topsy 480).  In  one  (Autopsy  467)  instance  an  abscess 
which  had  ruptured  into  the  pleural  cavity  had  completely 
discharged  its  contents  and  was  in  process  of  healing, 
newly  formed  fibrous  tissue  being  abundant  in  its  wall. 

With  few  exceptions  empyema  has  accompanied  sub- 
pleural  abscess  caused  by  hemolytic  streptococci,  being- 
found  on  the  side  corresponding  to  the  abscess.  Among 
39  instances  of  pulmonary  abscess,  empyema  has  been 
limited  to  the  side  of  the  abscess  in  23 ;  it  has  been  present 
on  the  opposite  side  as  well  in  10  instances.  In  2  instances 
there  have  been  abscesses  in  both  lungs;  in  one  (Autopsy 


234      PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATOR'S   TRACT 

385  A)  there  lias  been  double  empyema,  and  in  the  other 
(Autopsy  487)  empyema  only  on  the  left  side.  In  one  in- 
stance abscess  lias  been  recognized  by  microscopic  exami- 
nation and  iis  location  is  not  recorded.  In  5  instances  of 
abscess  formation  there  lias  been  no  empyema.  In  Autopsy 
.'!">.'!  there  lias  been  no  pleurisy  noted:  in  Autopsy  41(i  there 
lias  been  fibrinous  pleurisy  and  in  Autopsies  1*77,  290  and 
.'Nc.  serofibrinous  pleurisy. 

Empyema  has  been  almost  invariably  found  in  associa- 
tion with  interstitial  suppurative  pneumonia.  This  lesion 
extends  by  way  of  the  lymphatics  np  to  the  pleural  surface 
and  is  often  more  conspicuous  just  below  the  pleura  than 
elsewhere.  Empyema  has  been  absenl  in  only  3  of  21  ex- 
amples of  the  lesion  and  in  one  of  these  there  has  been 
serous  effusion.  In  12  instances  interstitial  suppuration 
has  occurred  only  on  one  side  and  empyema  has  been  lim- 
ited to  this  side;  in  5  instances  with  interstitial  suppura- 
tion on  one  side  there  has  been  empyema  on  both  sides; 
in  l!  instances  with  interstitial  suppuration  in  both  lungs 
there  has  been  double  empyema. 

The  amount  of  fluid  in  the  pleural  cavity  lias  varied  from 
less  than  100  to  1,500  c.c.  The  fluid  has  occasionally  been 
seropurulent  or  yellow,  thick  and  purulent,  but  in  most 
instances  the  exudate  is  best  described  as  fibrinopurulent. 
There  is  ycIIoav  or  yellowish  gray  purulent  fluid  contain- 
ing flakes  of  soft  ragged  fibrin. 

The  foregoing  study  has  shown,  on  the  one  hand,  that 
empyema  is  a  frequent  complication  of  streptococcus  pneu- 
monia and,  on  the  other  hand,  that  empyema  following  in- 
fluenza with  relatively  few  exceptions  is  caused  by  hemo- 
lytic streptococci.  Empyema  caused  by  this  microorgan- 
ism exhibits  in  some  instances  characters  not  seen  with 
other  varieties  of  pleural  inflammation.  The  tissue  be- 
tween sternum  and  pericardium  is  often  edematous  and  the 
adjacent  fat  has  a  firm  brawny  consistence.  Tn  some  in- 
stances the  exudate  contains  blood,  and  hemolysis  has  oc- 


PATHOLOGY  AND  BACTERIOLOGY    FOLLOWING    [NFLUENZA     235 

curred  so  that  the  fluid  has  a  diffuse  red  color.  The  occur- 
rence of  multiple!  pocketed  collections  of  purulent  fluid 
within  the  pleural  cavity  is  peculiar  to  streptococcus  empy- 
ema. These  pockets  have  been  found  6  limes  in  association 
with  abscess  and  5  times  with  interstitial  suppurative  pneu- 
monia. In  the  presence  of  an  exudate  within  the  pleural 
cavity,  some  part  of  the  lung,  usually  the  anterior  surface 
behind  the  sternum  and  costal  cartilages,  is  glued  by  fibrin- 
ous adhesions  to  the  parietal  pleura.  Here  occur  pockets 
containing  thin  purulent  fluid  and  softened  fibrin  or  thicker 
creamy  pus  walled  off  by  fibrin  about  the  edges  of  the 
pocket.  At  the  site  of  the  lesion  the  lung,  after  it  is  sepa- 
rated from  the  chest  wall,  is  marked  by  a  shallow  depres- 
sion surrounded  by  the  fibrin  which  has  walled  in  the 
pocket.  The  little  cavity  thus  formed,  varying  much  in 
size,  is  usually  oval,  the  long  diameter  being  from  1  to  3  cm. 
These  pleural  pockets  may  occur  over  the  external  sur- 
face of  the  lung  (Autopsies  452,  455,  and  472)  or  between 
the  internal  surface  and  pericardium  (Autopsy  452).  Oc- 
casionally with  partial  fibrinous  adhesion  between  the  pleu- 
ral surfaces  there  are  both  scattered  pockets  containing 
purulent  fluid  and  a  larger  encapsulated  collection  of  fluid ; 
in  Autopsy  455  the  pleural  surfaces  were  adherent  and 
there  was  100  c.c.  of  purulent  fluid  encapsulated  in  a  space 
over  the  external  surface  of  the  lung,  12x8  cm.  In  Autopsy 
452  the  lower  part  of  the  pleural  cavity  was  encapsulated 
and  contained  650  c.c.  of  fluid.  This  tendency  of  empyema 
caused  by  S.  hemolyticus  to  form  encapsulated  pockets  is 
doubtless  of  considerable  importance  in  the  treatment  of 
the  condition. 

Stone,  Bliss  and  Phillips5  have  described  these  encap- 
sulated pockets  as  "subcostosternal  pus  pockets"  and  have 
maintained  that  they  are  formed  about  the  sternal  lym- 
phatic nodes.  "We  have  found  them  so  widely  scattered 
that  this  relation  seems  improbable. 

6Stone,   W.  J.,  Phillips.   B.   G.,   and  Bliss,  W.   P.:     A   Clinical   Study  of  Pneumonia  Based 
on  S71   Cases.  Arch.  Int.  Med.,   1918,  xxii,   409. 


236      PNEUMONIAS  AXU   INFECTIONS  OF   RESPIRATORS   TRACT 

Pneumococcus  Empyema. —  Empyema  occurred  in  asso- 
ciation with  pneumonia  referable  to  pneumococci  LO  times, 
once  with  Pneumococcus  1 1 :  (5  times  with  Pneumococcus 
atypical  11:  once  with  Pneumococcus  111  and  twice  with 
Pneumococcus  [V.  The  lesion  was  seropurulent  once: 
fibrinopurulenl  8  times  and  purulent  once.  Fibrin  in  sev- 
eral instances  was  somewhal  voluminous.  In  the  following 
instance  voluminous  masses  of  fibrin  had  an  important  in- 
fluence upon  the  attempted  treatment. 

Autopsy  473. — A.  D.  P.,  white,  aged  twenty-one,  a  student  from  IWis- 
souri,  had  been  in  military  service  two  weeks.  He  was  admitted  to  the 
hospital  with  influenza  twenty-eight  days  before  his  death,  and  four  days 
after  admission  there  were  signs  of  pneumonia.  Paracentesis  was  per- 
formed mi  the  righl  side  on  the  eleventh  day  after  admission;  4  c.c.  of 
cloudy  fluid  which  contained  Pneumococcus  III  were  obtained  at  this  time 
and  later  in  the  day  800  c.c.  were  withdrawn.  On  the  thirteenth  day  at- 
tempted  withdrawal  of  fluid  from  both  pleural  cavities  failed.  On  the 
eighteenth  day  aspiration  of  the  right  pleura]  cavity  yielded  only  30  c.c. 
of  fluid.  On  the  nineteenth  day  400  c.c.  of  purulent  fluid  were  withdrawn 
from  the  right  pleural  cavity.  On  the  twenty-fifth  day  there  was  cyanosis 
and  delirium,  shortly  before  death  aspiration  of  the  right  pleural  cavity 
was  attempted,  luit  only  4  c.c.  of  fluid  were  obtained. 

Anatomic  Diagnosis. — Chronic  bronchopneumonia  with  lobular  and  peri- 
bronchiolar consolidation  in  left  lung;  flbrinopurulent  pleurisy  on  both 
sides;  purulent  bronchitis  and  bronchiectasis. 

On  removal  of  the  sternum,  encysted  purulent  pleurisy  is  found  be- 
tween the  inner  surface  of  the  right  lung  and  the  pericardium;  there  is 
here  450  c.c.  of  very  thick  creamy,  greenish  yellow  pus  entirely  separated 
from  the  remainder  of  pleural  cavity.  The  external  part  of  the  cavity 
contains  1,450  c.c.  of  fluid  and  voluminous  masses  of  firm  fibrin  which 
placed  in  a  measuring  cylinder  occupy  450  c.c.  The  left  pleural  cavity  con- 
tains 400  c.c.  of  seropurulent  fluid  in  which  there  is  abundant  sediment 
of  fibrinous  particles. 

The  right  lung  is  compressed;  the  bronchi  exude  purulent  fluid.  The 
left  lung  is  voluminous;  in  the  upper  and  lower  lobes  there  are  small  yel- 
lowish gray  nodules  of  consolidation,  grouped  in  (dusters,  and  gray  patches 
of  lobular  consolidation  occur.  Bronchi  are  dilated  and  filled  with  puru- 
lent fluid. 

I'.acteriologic  examination  shows  the  presence  of  Pneumococcus  III  ob- 
tained in  pure  culture  from  the  blood  of  the  heart  and  from  the  right 
pleural  cavity.  S.  viridans  is  grown  from  the  left  lung;  a  plate  from  the 
right  bronchus  contained  B.  influenzae,  S.  viridans  and  a  few  colonies  of 
staphylococcus  and  M.  catarrhalis. 


PATHOLOGY  AND  BACTERIOLOGY  FOLLOWING   I  X  I'M'KXZA     237 

The  foregoing  case  is  particularly  noteworthy  because 
aspiration  failed  repeatedly  to  yield  more  than  a  few  cuhic 
centimeters  of  fluid,  doubtless  because  the  voluminous 
masses  of  fibrin  present  in  the  cavity  prevented  escape  of 
fluid.  Aspiration  was  attempted  shortly  before  death,  but 
only  4  c.  c.  of  fluid  were  obtained;  nevertheless,  at  autopsy 
the  right  pleural  cavity  contained  2,350  c.c.  of  exudate.  An- 
other factor  of  much  importance  in  relation  to  treatment 
is  the  encapsulation  of  450  c.c.  of  purulent  fluid  between  the 
inner  surface  of  the  right  lung  and  the  pericardium.  It  is 
possible  that  free  drainage  might  have  emptied  the  main 
cavity  and  perhaps  even  freed  the  encapsulated  fluid. 

Pericarditis. — Among  241  autopsies  on  individuals  with 
pneumonia  following  influenza,  pericarditis  occurred  23 
times ;  these  lesions  were  classified  as  follows :  Serous  peri- 
carditis, 1 ;  serofibrinous  pericarditis,  9 ;  seropurulent  peri- 
carditis, 1 ;  fibrinopurulent  pericarditis,  10 ;  purulent  peri- 
carditis, 2. 

It  is  noteworthy  that  in  12  of  23  instances  of  pericarditis 
the  lesion  was  associated  with  S.  hemolyticus  infection  of 
the  lung  and  whenever  in  these  instances  cultures  were 
made  (Autopsies  434,  485,  499  and  504)  hemolytic  strepto- 
cocci were  obtained  from  the  pericardial  exudate  in  pure 
culture. 

The  tendency  of  interstitial  suppurative  pneumonia  to 
produce  pericarditis  is  especially  evident.  Among  21  in- 
stances of  interstitial  suppurative  pneumonia  pericarditis 
occurred  6  times  (28.6  per  cent) ;  among  39  instances  of  sup- 
purative pneumonia  with  abscess  formation,  pericarditis 
occurred  twice  (5.1  per  cent) ;  whereas  among  all  other 
autopsies,  namely,  181,  the  lesion  occurred  15  times  (8.3  per 
cent). 

Pericarditis  occurred  in  association  with  pneumonia  re- 
ferable to  Pneumococcus  I,  once,  (Pneumococcus  I  isolated 
from  the  pericardium) ;  to  Pneumococcus  II,  once ;  to  atypi- 
cal Pneumococcus  II,  5  times  (twice  isolated  from  the  peri- 


238      PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATOR?  TRACT 

cardium) ;  and  to  Pneumocoecus  IV.  twice  (once  isolated 
Prom  the  pericardium). 

Peritonitis. — Purulent  peritonitis  occurred  only  twice, 
in  both  instances  in  association  with  pneumonia  caused  by 
hemolytic  streptococci.  Purulenl  peritonitis  was  part  of 
a  genera]  serositis  involving  both  pleural  cavities,  peri- 
cardium and  peritoneum  in  2  noteworthy  instances: 

Autopsy  465. — J.  EL,  white,  aged  twenty-two,  farmer  from  Oklahoma, 
had  been  in  military  service  one  month.  He  \\  :i s  admitted  to  the  hospital 
with  influenza,  sore  throal  and  bronchitis  twenty-four  days  before  his 
death.  Signs  of  pneumonia  were  recognized  thirteen  days  later  and  at  the 
same  time  there  was  otitis  media  on  the  righl  side.  Empyema  and  peri- 
carditis were  found  three  days  before  death  and  two  days  later  looo  c.c. 
of  cloudy  fluid  were  withdrawn  from  the  chest. 

Anatomic  Diagnosis. — Suppurative  pneumonia  with  consolidation  and 
abscess  in  right  lower  lobe  below  pleura;  purulent  pleurisy  on  right,  sero- 
j. undent  pleurisy  on  left  side:  beginning  serofibrinous  pericarditis;  fibrino- 
purulent  peritonitis;   purulent  bronchitis. 

The  body  is  emaciated.  The  right  pleural  cavity  contains  350  <-.<■.  of 
thick,  creamy  yellow  pns  in  which  are  Hakes  of  fibrin;  the  right  lung 
is  collapsed  and  lies  at  the  back  and  inner  side  of  the  cavity.  The  lefl 
pleural  cavity  contains  .100  c.c.  of  turbid,  yellow,  seropurulent  fluid  in  which 
is  soft  fibrin.  The  lower  lobe  of  the  right  Inn-  is  consolidated  throughout, 
flabby,  gray  red  and  finely  granular  on  section.  Below  the  pleura  of  the 
posterior  border  is  a  wedge-shaped  cavity  with  its  base  1.5  em.  across,  in 
contact  with  the  pleural  surface.  About  the  cavity  consolidated  tissue  has 
an  opaque,  yellow  color.  Bronchi  in  both  lungs  contain  mucopurulent  fluid. 
The  pericardial  cavity  contains  20  c.c.  of  turbid  fluid;  the  left  auricular 
appendage  is  bound  by  a   thin  layer  of  fibrin  to   the  parietal  pericardium. 

The  peritonea]  cavity  contains  100  c.c.  of  thick,  creamy,  yellow,  purulent 
fluid.  Between  the  diaphragm  and  liver  is  a  layer  of  fibrin,  in  places  1.5 
cm.  in  thickness:  fibrin  is  present  upon  the  peritoneum  overlying  the  kidneys 
and   base   of  mesentery. 

Bacteriologic  examination  shews  the  presence  of  hemolytic  streptococci, 
obtained  in  pure  culture  from  the  blood  of  the  heart,  right  pleural  cavity 
and  peritoneum.  From  the  right  bronchus  are  grown  S.  hemolyticus,  B. 
influenza'    and    a    few    colonies   of   S.    viridans   and    staphylococcus. 

Autopsy  504. —  Gr.  El.  <  '.,  white,  aged  twenty-eight,  farmer  from  Alabama, 
had  1 n  in  military  service  three  months.  Onset  of  illness  occurred  six- 
day-    before    death,   ami    two   days   later    he    entered    the   hospital    with    fever 

-  In.",.  |     F.  ),  pains  in  the  abd< sn  and  vomiting.     Con  si  did  at  ion  at  the  bases 

of  the  lung  was  recognized  on  the  day  following  admission  and  on  the  day 
before  death  000  r.r,  of  greenish  brown  fluid  were  aspirated  from  the  left 
pleural   ca\  Lty. 


PATHOLOGY  AND  BACTERIOLOGY    FOLLOWING    I  X  KM  '  KN'XA     239 

Anatomic  Diagnosis. — Interstitial    suppurative   pneumonia    with   eon  oli 
elation   in   left   lower    lobe;    purulent    pleurisy    on    both    Hides;    purulent    peri- 
carditis;   purulent    peritonitis;    parenchymatous    degeneration    of    kidneys; 
acute  splenic  tumor. 

The  body  is  that  of  a  large  well- nourished  man.  The  lefl  pleural  cavity 
contains  975  c.c.  of  creamy,  yellow  fluid;  right  pleural  cavity  contains  425 
c.c.  of  purulent  fluid  thinner  than  that  on  the  lefl  side.  The  lefl  lung 
is  collapsed;  the  posterior  and  lower  half  of  the  lower  lobe  is  consolidated, 
flabby,  deep  rod  and  fleshy  in  appearance.  The  interstitial  septa  are  yel- 
low, thickened  with  bead-like  enlargements  and  contains  creamy  purulent 
fluid  which  flows  away  and  leaves  small  cavities.  This  interstitial  sup- 
puration is  more  advanced  below  the  outer  surface  of  the  lobe  than  else- 
where. 

The  pericardial  cavity  contains  25  c.c.  of  creamy,  yellow,  purulent, 
fluid;  the  epicardium  is  dull,  covered  in  a  few  places  by  a  small  amount 
of  fibrin   and  below  it  are  ecchymoses. 

The  peritoneal  cavity  contains  100  c.c.  of  thick,  yellow  pus;  the  peri- 
toneal surfaces  are  injected  and  between  the  liver  and  diaphragm  is 
fibrin. 

Bacteriologic  examination  shows  the  presence  of  S.  hemolyticus  in  pure 
culture  from  the  blood  of  the  heart,  the  lower  lobe  of  the  left  lung,  peri- 
cardium and  peritoneum.  The  right  main  bronchus  contains  the  same 
microorganism,  B.   influenzae   and   a   few   staphylococci. 

General  serositis  lias  been  caused  by  hemolytic  strep- 
tococci which  in  one  instance  have  entered  the  pleura  from 
a  snbpleural  abscess,  and  in  the  other  from  the  suppurating 
interstitial  tissue  of  the  lung.  In  one  of  these  cases  the 
patient  entered  the  hospital  with  symptoms  suggestive  of 
acute  peritonitis. 

Bronchiectasis 

Acute  dilatation  of  the  bronchi  is  a  common  result  of 
the  bronchitis  of  influenza,  and  its  frequent  occurrence  is 
an  index  of  the  severity  of  the  changes  in  the  bronchial 
wall.  In  some  instances  the  smaller  bronchi  in  well-local- 
ized areas  are  uniformly  dilated;  in  other  instances,  large 
cavities,  several  centimeters  in  diameter,  are  formed  and 
all  transitions  between  the  two  extremes  occur. 

The  occurrence  of  bronchiectasis  following  influenza  is 
mentioned  by  Leichtenstern6.     He  states  that  evidence  of 

«I,oc.   cit.,   p.    110. 


240    rxi:r.M<>xiA>  and  infections  of  respirator's  tract 

bronchiectasis  can  persisl  for  weeks  or  months  and  never- 
theless end  with  complete  restitution  of  the  lungs  to  normal. 
Lord7  lias  (described  instances  of  bronchiectasis  occurring 
in  association  with  infection  by  B.  influenzae  and  Boggs8 
has  recorded  similar  observations. 

We  have  had  abundant  opportunity  to  observe  early 
stages  in  the  production  of  bronchiectasis  and  to  study  the 
much  discussed  pathogenesis  of  the  condition. 

The  following  figures  show  the  predilection  of  bronchiec- 
tasis Tor  the  left  lung  and  for  the  lower  lobes:  Bronchiec- 
tasis occurred  30  times  in  the  left  lung  alone,  9  times  in 
the  right  lung  alone  and  13  times  in  both  lungs,  the  total 
being  52.  Among  30  instance's  in  which  the  lesion  occurred 
only  in  the  left  lung,  in  24  it  was  limited  to  the  lower  lobe, 
and  in  15  of  these  24  instances  to  the  base  of  the  lower  lobe. 
Among  9  instances  in  which  dilatation  oC  bronchi  occurred 
only  in  the  right  lung,  it  was  limited  to  the  lower  lobe  in 
4  instances  and  to  the  base  of  the  lower  lobe  in  2  of  these 
4  instances. 

When  the  lesion  is  limited  to  the  base  of  the  lower  lobes 
small  bronchi  with  no  recognizable  cartilage  in  their  wall 
are  dilated  to  a  diameter  of  from  3  to  6  cm.  and  are  dis- 
tended with  thick  mucopurulent  fluid.  The  tenacious  char- 
acter of  the  bronchial  contents  and  the  action  of  gravity 
doubtless  have  a  part  in  the  production  of  the  dilatation. 
In  several  instances  dilatation  of  the  bronchi  was  limited 
to  the  basal  parts  of  both  upper  and  lower  lobes. 

When  bronchiectasis  occurs  throughout  a  whole  lung, 
usually  the  left,  or  in  both  lungs,  the  lesion  is  more  ad- 
vanced and  conspicuous  (Fig.  26).  There  is  diffuse  dila- 
tation of  small  and  medium-sized  bronchi.  Dilated  bronchi 
with  deeply  injected  mucosa  and  filled  with  yellow  muco- 
purulent fluid,  are  seen  throughout  the  sectioned  lung.  A 
bronchus  cut  longitudinally  may  have  a  nearly  uniform 


7Lord,    F.    T.:     Infections    of   the    ■Respiratory    Tract    with    Influenza    Bacilli,    Boston    Med. 

and   SurR.  Jour.,   1905,  clii.   537.   574. 
sBoggs,  T.  R. :  Influenza  Bacillus  in  Bronchiectasis,  Am.  Jour.  Med.  Sc,  1905,  exxx,  902. 


PATHOLOGY  AND  BACTERIOLOGY   FOLLOWING    I  X  I  U 'K.\ZA     241 

diameter  of  from  5  to  9  mm.  for  a  distance  of  5  or  6  cm., 
maintaining  this  diameter  to  within  1  cm.  of  the  pleural 
surface,  where  normally  only  small  bronchi  occur. 

More  advanced  bronchiectasis  is  represented  by  the  oc- 
currence of  spherical  bronchiectatic  cavities,  having  a 
diameter  from  1  to  2.5  cm.  In  some  instances  there  have 
been  two  or  three  of  these  cavities  but  occasionally  there 
may  be  many.  Cylindrical  dilatation  of  the  bronchi  usu- 
ally occurs  widely  distributed  in  the  lungs.  In  Autopsy 
440  a  small  bronchus,  cut  longitudinally,  was  dilated  to  a 
diameter  of  5  mm.  for  a  distance  of  5  cm.  and  terminated 
in  a  spherical  cavity  2  cm.  in  diameter;  there  was  another 
smaller  spherical  cavity  nearby  and  dilated  bronchi  oc- 
curred elsewhere.  In  Autopsy  467,  in  the  upper  part  of 
the  lower  lobe,  two  spherical  cavities  1  and  1.5  cm.  in  diame- 
ter communicated  with  a  bronchus  of  medium  size. 

Autopsies  with  bronchiectasis  are  listed  in  the  order  of 
the  duration  of  illness  to  show  the  parallel  increase  in  the 
severity  of  the  lesion  (Table  LI).  In  2  instances  (Autopsies 
244  and  314)  bronchiectatic  cavities  surrounded  by  firm 
fibrous  tissue  have  evidently  existed  before  the  onset  of  the 
fatal  illness,  which  has  lasted  in  one  instance  approximately 
four  and  in  the  other  six  days;  these  autopsies  have  been 
omitted  from  the  table. 

The  table  shows  that  bronchiectasis  observed  within 
twelve  da}7s  after  onset  of  illness  with  symptoms  of  influ- 
enza is  moderately  advanced  and  almost  invariably  limited 
to  the  left  lower  lobe  and  usually  to  the  base  of  the  lobe. 
Advanced  dilatation,  indicated  by  the  formation  of  spheri- 
cal or  cylindrical  cavities,  occurs  with  increasing  frequency 
as  the  duration  of  the  respiratory  disease  increases. 

Bronchiectasis  has  been  almost  invariably  associated 
with  purulent  bronchitis.  The  dilated  bronchi  contain  mu- 
copurulent material  and  throughout  the  lungs  the  same  con- 
dition is  usually  widespread.  Among  137  instances  of  pur- 
ulent bronchitis  bronchiectasis  consequent  upon  influenza 
has  been  present  in  50. 


242      PNEUMONIAS  AND   INFECTIONS  OF   RESPIRATORS  TRACT 

Table  LI 


1 

DURATION 

0<    ITION 

CHAB  UTKK 

OP 

T\ PE   OF 

OT    BRON- 

OF   BRON- 

BACTERIA    IN 

NO.  OF 

Il,l.~. 

PNEUMON]  \ 

CHIECTASIS 

CHIECTASIS 

BRONCHUS 

AUTOPSY 

IN    DAYS 

394 

5   ? 

Broncho 

Rt.  base 

Dilatation 

359 

7  + 

Lobar  and 
broncho 

l.i.  lower  lob( 

Dilatation 

322 

8 

Abscess 

ph.) 

Lt.  1  ase 

Dilatation 

325 

8 

[nterst.    sup 
pural  ion 

I.t.  base 

Dilatation 

S.     hem., 

B.   inf., 
staph. 

352 

8 

Lobar   and 
broncho 

Lt.  lower  lobe 

Advanced 

dilatation 

429 

8    .' 

Broncho 

Rt.  base 

1  >ilatation 

288 

LO 

Abscess 

Lt.  base 

Dilatation 

s.  hem., 
B.  inf. 

374 

10 

Lobar  and 

Rt.  and  It. 

Advanced 

broncho 

lungs 

dilatation 

376 

in 

Abscess 

Lt.    base 

Dilatation 

S.    hem. 

437 

n 

Lobar 

Rt.  lower  lobi 

Ad\  anced 

dilatation 

182 

n 

Broncho 

Lt.  base 

Dilatation 

B.  inf., 

Taenia.    IV. 
S.   hem. 

489 

11 

Lobar  and 
broncho 

Lt.  lung 

I  >  il  at  ati  on 

B.   inf., 
Pneum.  IV. 

287 

12 

Lobar  and 

Lt.  lower  lobe 

Advanced 

Pneum.    IV.. 

]  ironcho 

dilatation 

B.   inf., 

staph. 

289 

12 

Broncho 

Lt.    lower    Ink 

Advanced 

Pneum.    IV., 
B.    inf. 

staph. 

295 

12 

[nterst.  sup. 

Rt.  lung 

Advanced 

S.    hem.. 

and  abscess 

dilatation 

B.  inf. 

336 

12 

Broncho 

Lt.  bass 

Dilatation 

375 

12 

Broncho 

Rt.  and  lt. 

liases 

Dilatation 

422 

12    .' 

Lobar  and 
broncho 

Lt.  base 

1  Mlatation 

381 

13 

Abscess 

Lt.  base 

Spherical 

391 

13 

Lobar  and 
broncho 

Lt.  lung 

I  dilatation 

40] 

14    ? 

Lobar  and 
broncho 

Rt.  and  lt. 

1 1 1 1 1  g  s 

.Spherical 

402 

14 

Chronic 
broncho 

Rt.  lower  lobe 

1  dilatation 

410 

1  1    .' 

Abscess 

Rt.  upper  lobe 

1  dilatation 

333 

15 

Al>sc.  ss 

(staph.) 

Lt.  upper  lobi 

1  (ilatation 

S.  aur.,  B. 
inf.   8.   hem. 

389 

1.1 

[nterst.    sup 
pural  inn 

Lt.  lung 

Advanced 

dihitat  ion 

412 

l.l 

Lobar  and 
broncho 

Lt.   lower  lobi 

Cylindrical 

398 

16 

Broncho 

Rt.  and  It. 
lungs 

Advanced 

dilatat  ion 

423 

16 

Broncho 

Lt.  base 

Dilatation 

PATHOLOGY  AND  BACTERIOLOGY  FOLLOWING  INFLUENZA     243 

Table  LI — Cont'd 


DURATION 

LOCATION 

.     CHARACTER 

NO.  OF 

OF 

TYPE    OF 

OF    BRON- 

OF  BRON- 

BACTERIA   IN 

AUTOPSY 

ILLNESS 

PNEUMONIA 

BRO    ( in  a 

IN    DAYS 

CHIECTASIS 

CHIECTASIS 

488 

16 

Abscess 

Lt.  lower  lob< 

1  >il;ita1  ion 

8.   Item., 
Pneum. 
atyp.  II., 

312 

17 

Broncho 

Rt.  and  It. 

lungs 

Dilatation 

S.   hern.,   B. 
inf. 

staph. 

372 

17 

"Broncho 

Rt.    lung 

Dilatation 

385  C 

17 

Interst.  sup- 
puration 

Lt.  base 

Dilatation 

448 

17 

Broncho 

Lt.  lung 

Dilatation 

460 

17 

Abscess 

Lt.  lower  lobe 

Spherical 

S.  hem.,  B. 
inf.,  staph. 

291 

18 

Broncho 

Lt.  base 

Ad  van  cod 
dilatation 

B.  inf., 
staph. 

296 

18 

Abscess 

Lt.  base 

Dilatation 

S.  hem.,  B. 
inf., 

387 

19 

Abscess 

Rt.   and   lt. 

Advanced 

S.  hem.,  B. 

lungs 

dilatation 

inf.,   S.   a"r. 
Pneum.   II. 

421 

19 

Chronic . 
broncho 

Rt.  lung 

Advanced 
dilatation 

440 

19 

Chronic 

Rt.  and  lt. 

Spherical 

B.    inf.,    S. 

broncho 

lungs 

aur. 

419 

20 

Broncho 

Rt.  lung 

Dilatation' 

Pneum.  II, 
B.   inf. 

463 

20 

Chronic 

Rt.  and  lt. 

Spherical 

B.   inf., 

broncho 

lungs 

staph., 
Pneum.   IV 

431 

23 

Chronic 
broncho 

Lt.  base 

Dilatation 

468 

23   ? 

Lobar  and 
broncho 

Lt.  lung 

Dilatation 

S.  aur.,  B. 
inf.,    S.   vir. 

465 

25   ? 

Broncho 

Lt.  base 

Dilatation 

S.  hem.,  B. 
inf.,   staph., 
S.    vir. 

445 

27 

Broncho 

Lt.  lower  lobe 

Spherical 

S.   aur. 

449 

27 

Abscess 

Rt,  and  lt. 
lungs 

Spherical 

S.   hpm.,  B. 
coli. 

378 

28 

Abscess 

Lt.   base 

Cylindrical 

S.  hem.,  B. 
inf., 
P'neum. 
atvp.  II. 

473 

28 

Chronic 

Lt.   lung 

Advanced 

B.  inf.,   S. 

broncho 

dilatation 

vir.,   staph., 
M.    catarr. 

425 

29 

Abscess 
(staph.) 

Rt.  and  lt. 
lungs 

Cylindrical 

467 

30 

Abscess 

Rt.  lower  lobe 

Spherical 

S.  hem., 
B.  inf. 

472 

37 

Chronic 

Rt.  and  It. 

Advanced 

B.  coli 

broncho 

lungs 

dilatation 

487 

55 

Abscess 

Rt.  and  It. 

lungs 

Cylindrical 

B.  inf.  S. 
hem. 

244      PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATOR?  TRACT 

The    bacteriology    of   autopsies    with    bronchiectasis    is 
shown  in  Table  LII. 


Table  LII 

Q 

x 

a 

.  - 

O     X 

x   w 

PNEU- 

Mm   01   CI    - 

S.  HEMOLY- 
TICUS 

STAPHY- 
LOCOCCUS 

B.  1XKUT.NZ.K 

E 

2    I 

X      > 

-  a 

-  c 

> 
■- 

_•      BG 
-      O 

X         pi, 

£  5 

3  E 

EH 

_•     /. 
O     o 
X     Ph 

b  i 

11 

w 
j> 

O     o 
X     P, 

S  2 

Bronchus 
Lung 

Blood 

29 
37 
50 

9 

16 
12 

31.0 
43.2 

24.0 

15 

18 

.i.i 

51.7 
t8.6 

44.0 

16 

10 

55.2 

27.0 

23 

lit 

7!».:: 
51.4 

Comparison  of  the  percentage  incidence  of  the  organisms 
which  have  to  be  found  associated  with  bronchiectasis  and 
with  purulent  bronchitis  unaccompanied  by  bronchiectasis 
shows  that  there  is  no  noteworthy  difference  in  the  occur- 
rence of  pneumococci,  hemolytic  streptococci  or  B.  influ- 
enzae within  the  bronchi.  When  allowance  is  made  for  the 
difficulty  of  demonstrating  B.  influenzae  in  the  presence  of 
a  large  number  of  other  microorganisms,  it  is  not  improb- 
able thai  this  organism  lias  been  constantly  present  in  the 
purulent  contents  of  the  bronchi  with  purulent  bronchitis, 
with  and  without  bronchiectasis.  Pneumococci,  strepto- 
cocci and  staphylococci  are  each  present  in  the  bronchi  in 
about  one-half  of  the  instances  of  bronchiectasis  and  mixed 
infections  are  very  common,  S.  viridans,  B.  coli  and  M. 
catarrhalis  being  occasionally  Pound  in  the  bronchi.  The 
table  shows  that  pneumococci,  streptococci  and  staphyl- 
ococci show  no  greater  tendency  to  enter  the  lungs  and 
blood  when  bronchiectasis  and  purulent  bronchitis  coexist 
than  with  purulent  bronchitis  alone. 

.Moderate  dilatation  of  the  small  bronchi  at  the  base  of 
the  left  lung  was  round  in  several  instances  eight  days 
after  onset  of  symptoms  referable  to  the  respiratory  pass- 
ages. Advanced,  diffuse  dilatation  of  the  bronchi  was 
seldom  seen  before  the  lapse  of  two  weeks,  and  bronchiec- 
tasis with   formation  of  spherical   or    cylindrical    cavities 


PATHOLOGY  AND  BACTERIOLOGY    FOLLOWING    I  X  I'M 'KX/A     245 

was  found  with  few  exceptions  three  weeks  after  onsel  of 
the  fatal  illness.  Long  continued,  purulent  bronchitis  does 
not  necessarily  produce  dilatation  of  the  bronchi.  It  is 
noteworthy  that  the  average  duration  of  the  fatal  illness 
in  137  instances  of  pneumonia  and  purulent  bronchitis  with 
no  bronchiectasis  was  12.5  days,  Avhereas  the  average  dura- 
tion of  49  instances  of  pneumonia  with  purulent  bronchitis 
and  bronchiectasis  was  only  16.5  days. 

Bronchiectasis  is  almost  invariably  associated  with  pur- 
ulent bronchitis  in  which  tenacious  mucopurulent  fluid  ac- 
cumulates in  the  bronchi.  It  begins  at  the  bases  of  the 
lower  lobes  and  is  usually  more  advanced  here  than  else- 
where. Mechanical  distention  of  the  small  bronchi  by 
viscid  fluid,  expelled  with  difficulty,  brings  about  their  dila- 
tation and  gravity  appears  to  have  a  part  in  accentuat- 
ing the  process.  Histologic  examination  of  the  changes 
accompanying  bronchitis  show  that  lesions  which  penetrate 
into  the  muscular  layer  and  presumably  weaken  the  bron- 
chial wall  are  not  uncommon  and  partial  or  complete  de- 
struction of  the  wall  may  result.  To  what  extent  infiltra- 
tion of  the  muscular  wall  by  polynuclear  leucocytes  or  by 
lymphoid  and  plasma  cells  is  accompanied  by  changes  which 
weaken  the  wall  may  be  questioned.  When  the  epithelial 
lining  of  the  bronchus  is  destroyed  coagulative  necrosis  of 
the  underlying  tissue  occurs  and  may  extend  a  variable 
distance  into  the  bronchial  wall,  not  infrequently  pene- 
trating into  or  entirely  through  the  muscular  layer.  These 
changes  furnish  an  explanation  of  the  occurrence  of  bron- 
chiectasis following  influenza. 

Acute  bronchiectasis  may  be  found  following  influenza 
after  the  illness  has  lasted  eight  or  ten  days.  There  is  no 
increase  of  fibrous  tissue.  Small  bronchi  with  no  cartilage, 
which  in  normal  lungs  have  a  diameter  approximating  1 
mm.,  are  dilated  to  3  mm.  or  more.  The  surface  epithelium 
is  wholly  or  partially  lost.  Necrosis  occurs  in  places  and 
extends  deep  into  the  tissue,  destroying  muscle  and  often 


246      PNEUMONIAS  AND   INFECTIONS  OF   RESPIRATOR'S   TRACT 

penetrating  the  entire  thickness  of  the  wall  which  in  these 
small  bronchi  consists  in  large  part  of  fibrous  tissue  con- 
taining greatly  engorged  blood  vessels.  In  this  necrotic 
material  nuclei  are  absenl  and  the  tissue  containing  fibrin 
stains  deeply  with  eosin.  In  it  occur  fissures  or  tears  which 
extend  from  the  lumen  a  variable  distance,  very  frequently 
penetrating  the  entire  thickness  of  the  wall  and  entering 
adjacent   alveoli   (Figs.  17  and  10).     Alveoli  thus  exposed 


Fig.  17. — Acute  bronchiectasis  showing  fissures  penetrating  into  bronchial  wall  ami 
at  one  place  entering  surrounding  alveolar  tissue;  the  surrounding  alveoli  are  filled  with 
fibrin.     Autopsy  425. 


almost  invariably  contain  plugs  of  dense  fibrin.  Where 
these  rents  have  occurred,  adjacent  edges  of  the  bronchial 
wall,  held  together  by  underlying  lung  tissue,  have  sepa- 
rated from  one  another,  so  that  the  circumference  of  the 
bronchus  has  been  increased  (Fig.  18).  These  breaks  in 
the  continuity  of  the  wall  may  occur  in  several  places,  so 
that  a  fourth  or  a  third  of  the  circumference  maybe  formed 


PATHOLOGY  AND  BACTERIOLOGY    FOLLOWING    I  X  I'M  '  KXXA     247 


by  exposed  alveolar  tissue  which  has  become  the  site  of 
fibrinous  pneumonia  (Fig.  20).  During  life,  though  the  in- 
flamed bronchus  is  filled  by  mucopurulenl  exudate,  disten- 
tion of  loose  alveolar  tissue,  uniting  the  interrupted  bron- 
chial Avail,  is  doubtless  greater  than  it  appears  in  the  Lung 
fixed  by  hardening  fluids. 

Kecently  dilated  bronchi  have  an  irregularly  stellate  lu- 
men as  the  result  of  clefts  penetrating  at  intervals  into  or 


•^  -ft*  i/t 


-  > 


it 


'j&* 


SS&Ssfe; 


i^Sp* 


Fig.  18. — Acute  bronchiectasis  showing  fissures  in  the  bronchial  wall  extending  into 
neighboring  alveoli  which  in  zone  about  are  filled  with  fibrin;  one  fissure  has  separated 
widely;    peribronchial    fibrinous    pneumonia    (fibrin    is    black).     Autopsy    425. 

through  the  bronchial  wall  (Fig.  26) .     Longitudinal  fissures 
mark  the  lining  of  these  dilated  bronchial  tubes. 

When  the  fatal  illness  has  lasted  more  than  two  weeks, 
abundant  new  formation  of  fibrous  tissue  occurs  in  a  zone 
surrounding  the  dilated  bronchus.  Adjacent  alveolar  walls 
are  thickened  by  young  fibrous  tissue.  Alveoli,  much  di- 
minished in  size,  are  filled  by  hyaline  fibrin  into  which  fibro- 


248     PNEUMONIAS  AND   [NFECTIONS  OF  RESPIRATORY  TRACT 

blasts  and  aewly  formed  blood  vessels  have  penetrated. 
These  changes  are  limited  to  a  wide  /.one  in  immediate  con- 
tact with  the  dilated  bronchus,  whereas  at  a  greater  dis- 
tance  alveolar  walls  have  undergone  no  thickening  and 
alveoli  contain  no  fibrin. 


Fig.  19.— Acute  bronchiectasis;  the  bronchial  wall  indicated  by  engorged  mucosa  shows 
a  varying  degree  of  destruction,  fissures  extending  into  and  through  the  bronchial  wall. 
Autopsy   352. 


PATHOLOGY  AND  BACTERIOLOGY    FOLLOWING    INFLUENZA     2V.) 


This  stage  is  well  represented  by  Autopsy  421  after  an 

illness  of  nineteen  days.  Bsonchieetatic  cavities,  from  .'j 
to  6  mm.  in  diameter,  are  numerous  in  sections  of  the  lung; 
their  lumina  are  irregular  in  outline  and  often  irregularly 
stellate.     Microscopic  examination  shows  the  presence  of 


Fig.  20. — Acute  bronchiectasis;  with  destruction  of  bronchial  wall  exposing  alveoli 
filled  with  fibrin;  peribronchial  fibrinous  pneumonia  is  seen  about  several  bronchi  present 
in   the    section;    Gram-Weigert   fibrin   stain.     Autopsy    425. 


250      PNEUMONIAS  ANh   INFECTIONS  OF   RESPIRATOR'S   TRACT 

clefts  which  interrupt  the  bronchial  wall  a1  intervals 
throughout  its  entire  circumference.  The  original  wall  is 
well  indicated  by  the  very  richly  vascularized  connective 
tissue  containing  scattered  muscle  bundles  and  is  infil- 
trated with  Lymphoid  and  plasma  cells  in  greal  number. 
Where  fissures  have  occurred  the  adjacent  edges  of  the  in- 
terrupted wall  have  separated  Prom  one  another,  leaving 
a  wide  interval  where  underlying  alveolar  (issue  is  exposed. 
Two  changes  lend  eventually  to  render  the  fissures  incon- 
spicuous, namely,  regeneration  of  epithelium  and  new  for- 
mation of  fibrous  tissue.  Exposed  alveoli  filled  with  fibrin 
are  in  process  of  organization  and  epithelium  which  lias  as- 
sumed a  squamous  type  has  grown  down  over  the  exposed 
-in  faces  of  the  interrupted  bronchial  wall.  It  has  begun  to 
cover  or  in  some  instances  lias  completely  covered  the  sur- 
face of  rents  entering  alveoli  plugged  with  fibrin  (Fig.  21). 
In  the  periphery  of  the  bronchus  alveolar  walls  are  thick- 
ened and  infiltrated  with  lymphoid  and  plasma  colls.  The 
same  changes  affect  bronchi  containing  cartilage  which  is 
undergoing  atrophy. 

The  reinforcement  of  the  fissured  bronchial  wall  by  new 
formation  of  fibrous  tissue,  by  thickening  of  the  interalve- 
olar  walls  and  by  organization  of  fibrin  within  the  alveoli  is 
well  shown  after  four  weeks  (Autopsy  425;  Fig.  28). 
There  are  spherical  bronchiectatic  cavities  more  than  a  cen- 
timeter in  diameter  surrounded  by  a  dense  fibrous  Avail  in 
which  are  atrophied  alveoli  lined  by  epithelium  of  cubical 
form.  Occasionally,  the  fibrous  wall  is  interrupted  and  al- 
veoli, plugged  with  organizing  fibrin,  are  in  immediate  con- 
tact with  the  lumen.  When  these  plugs  of  fibrin  which  are 
slowly  absorbed  disappear,  evidence  of  preexisting  rents  in 
the  bronchial  wall  are  lost,  and  there  are  in  this  lung  bron- 
chiectatic cavities  of  which  the  wall  is  a  continuous  circle 
of  dense  fibrous  tissue. 

Epithelium  lining  the  dilated  bronchi  is  at  times  com- 
pletely destroyed  (Fig.  28),  but  more  frequently  it  persists 


PATHOLOGY  AND  BACTERIOLOGY  FOLLOWING  I  X  I'M  '  KXXA  25] 

in  part.  That  which  remains  has  almost  constantly  the 
character  of  squamous  epithelium  (Figs.  '2'2  and  23).  The 
lowermost  cells  arc  cubical;  those  above  them  are  poly- 
gonal, tending  to  become  flatter  as  the  surface  is  ap- 
proached; upon  the  surface  are  cells  often  much  flattened 
and  occasionally  they  have  lost  their  nuclei  and  slain  deeply 


Fig.  21. — Bronchiectasis  with  fissures  extending  through  the  bronchial  wall  into  alve- 
olar tissue  which  is  the  site  of  fibrinous  pneumonia;  epithelium  has  grown  down  into 
these  fissures  and   has  covered  the  exposed  surfaces.     Autopsy  463. 


252      PNEUMONIAS  A  Nli   INFECTIONS  OE  RESPIRATOR'S  TRACT 

with  eosiu  as  the  result  of  superficial  necrosis.  The  change 
should  not  be  regarded  as  metaplasia,  for  the  epithelium 
assumes  this  squamous  type  when  the  superficial  columnar 
cells  have  been  lost.  Actual  necrosis  of  superficial  ciliated 
columnar  cells  is  occasionally  seen  (Autopsy  352);  injured 
cells  have  separated   from  one  another  and  desquamated 


Fig.  22. — Regeneration  of  epithelium  over  fissures  which  have  been  formed  in  the  wall  of  a 
bronchus;  the  epithelium  in  the  neighborhood  of  and  within  the  fissure  is  squamous. 


PATTTOLOGY  AND  BACTERIOLOGY   FOLLOWING   INFLUENZA     253 

into  the  lumen  of  the  bronchus.  The  epithelium  which  re- 
mains after  the  superficial  cells  are  lost  consists  of  cells 
which  become  flatter  from  base  to  surface,  but  the  intercel- 
lular bridges  characteristic  of  the  epithelium  of  the  skin 
are  not  found.  When  epithelium  is  in  process  of  regenera- 
tion, a  layer  gradually  diminishing  in  thickness  extends 


.       «  ■~g  *  .,-•  *  u.    *  -'  <■.*  t  _^~  «•'«*«  »vj; 'i.i        & 


Fig.  23. — Squamous  epithelium  growing  over  the  defect  in  the  bronchial  wall  shown 
in  Fig.  22  more  highly  magnified;  squamous  epithelium  is  present  above  and  columnar 
epithelium   below. 


254      PNEUMONIAS  AXI>    I  X  l-T.CTloxs  OF   RESPIRATORY   TRACT 

over  the  denuded  surface,  the  advancing  edge  being  formed 
by  very  lint  cells  in  a  single  layer.  The  epithelium  grow- 
ing into  fissures  which  have  penetrated  the  bronchial  wall 
may  completely  cover  the  exposed  alveolar  tissue.  The 
newly  formed  epithelium  may  follow  a  fissure  into  an  alve- 
olus which  lias  been  opened  and  conic  into  contact  with  the 
fibrin  which  fills  the  alveolus. 

Bronchiectasis  usually  affects  the  small  bronchi  with  no 
cartilage.  It  is  not  uncommon  to  find  greatly  dilated  bron- 
chi with  no  cartilage  in  close  proximity  to  cartilage  con- 
taining bronchi  of  smaller  caliber.  In  one  instance  (Au- 
topsy 421)  a  bronchus  of  medium  size  with  cartilage  meas- 
ured 3  mm.  in  diameter,  whereas  two  bronchi  with  no  car- 
tilage were  dilated  to  4  and  0  mm.,  respectively.  Neverthe- 
less, larger  bronchi  are  occasionally  the  site  of  superficial 
loss  of  epithelium,  necrosis  extending  into  the  bronchial 
wall,  formation  of  fissures  and  si  retching  of  the  wall  at  the 
spot  which  is  weakened.  In  association  with  these  changes 
atrophy  of  the  cartilage  may  occur  (Autopsies  421,  425, 
440,  4(53).  Plates  of  cartilage  in  process  of  atrophy  are 
readily  recognized  by  their  irregularly  indented  outline 
and  often  by  their  small  size.  The  fibrous  tissue  surround- 
ing the  cartilage  is  the  site  of  chronic  inflammation  and  is 
densely  infiltrated  with  lymphoid  and  plasma  cells  among 
which  polynuclear  leucocytes  are  scant.  Nevertheless, 
polynuclear  leucocytes  are  abundant  in  immediate  contact 
with  the  cartilage  and  appear  to  have  an  important  part  in 
the  solution  of  its  matrix,  for  about  them  occur  indenta- 
tions of  the  edge.    Leucocytes  penetrate  into  the  cartilage. 

The  necrosis  and  tears  which  occur  in  the  wall  of  the 
bronchus  are  not  always  limited  to  the  bronchus,  but  may 
extend  deeply  into  the  surrounding  tissue.  In  Autopsies 
312  (Fig.  21)  and  423  wide  areas  of  necrosis  have  pene- 
trated deeply  into  the  tissue  about  the  bronchi. 

Autopsy  312. — Illness  began  with  influenza  on  September  26,  seventeen 
days    befoi-f   *  1  < • ; 1 1 1 1 :    ;i    diagnosis   <>f   lobar    pneumonia    with    consolidation    of 


PATHOLOGY  AND  BACTERIOLOGY    FOLLOWING    IXI  U'K.YXA 


255 


the  right  lower  lobe  was  made  ten  days  after  onset  and  Pneumococcua  IV, 
B.  influenzae  and  S.  hemolytieus  wore  found  in  the  sputum.  Af  autop  . 
there  was  bronchopneumonia  with  rod  and  gray  lobular  and  confluenl 
lobular  patches  of  consolidation  and  right  and  Lef1  serofibrinous  pleurisy; 
there  was  purulent  bronchitis;  no  abscesses  were  scon.  Small  bronchi 
throughout  both  lungs  were  dilated  and  often  surrounded  by  a  zone  of  hem- 
orrhage. 

Hemolytic  streptococci  were  found  in  the  heart's  blood,  in  the  pleural 
exudate,  consolidated  lung  and  bronchus;  B.  influenzee  was  found  in  the 
lung  and  in  a  small  bronchus,  and  staphylococci  in  the  contents  of  a  small 
bronchus. 


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Fig.  24. — Acute  bronchiectasis  with  fissures  extending  through  bronchial  wall  which 
is  marked  by  great  engorgement  of  blood  vessels;  at  one  point  a  fissure  has  penetrated 
deep  into  the  alveolar  tissue  and  formed  a  small  cavity  containing  purulent  exudate  and 
surrounded  by   fibrinous   pneumonia.     Autopsy   312. 


Bronchi  which  are  the  site  of  acute  inflammation  have  lost  their  epi- 
thelium wholly  or  in  part,  and  deep  fissures  penetrate  the  entire  thickness 
of  the  bronchial  wall,  extending  into  the  surrounding  lung  tissue  which  is 
the  site  of  fibrinous  pneumonia.  In  some  instances  plugs  of  fibrin  within 
the  alveoli  are  bisected  by  these  tears.  There  is  some  superficial  necrosis 
along  the  edge  of  each  fissure,  in  several  places  extending  outward  from 
defects  in  the  walls  of  small  bronchi  dilated  to  approximately  1.5  mm. 
There  are  wide  patches  of  necrosis  affecting  both  alveolar  walls  and  con- 


256      PNEUMONIAS  A.ND   [NFECTIONS  OF  RESPIRATORY  TRACT 

tints  of  alveoli  and  extending  2  nun.  into  the  lung  tissue.  When  a  fissure 
has  penetrated  from  the  lumen  of  the  bronchus  into  necrotic  tissue 
(Fig.  21),  polynuclear  leucocytes  have  accumulated  within  tin'  necrotic 
t issue,  disintegration  of  tissue  occurs,  and  a  small  cavity  communicating 
with  tin'  bronchus  is  formed. 

Autopsy  423. — ('.  11.,  white,  aged  twenty-live,  resident  of  Oklahoma, 
had  been  in  military  service  one  month.  Death  occurred  sixteen  days  after 
onset   of  influenza. 

Anatomical  Diagnosis. — chronic  bronchopneumonia  with  peribronchiolar 
consolidation  throughoul  righl  lung  and  in  left  lower  lose;  right  purulent 
pleurisy;   purulent   bronchitis;    bronchiectasis  at  base   of  left   lung. 

The  right  lung  weighs  1,260  grams;  in  the  upper  lobe  are  yellowish 
gray  nodules  having  the  appearance  of  tubercles  clustered  about  small 
bronchi;  in  places  similar  nodules  occur  upon  a  background  of  pinkish 
gray  consolidation  occupying  the  greater  part  of  the  lower  lobe.  Bron- 
chi contain  purulent  fluid.  The  left  lung  weighs  760  grams;  it  is  edema- 
tens  and  small,  yellowish  gray  nodules  of  consolidation  in  the  lower  lobe 
are  clustered  about  terminal  bronchi.  Bronchi  at  the  base  of  the  lower 
lobe  are  dilated. 

Bacteriologic  examination  shows  the  presence  of  hemolytic  streptococci 
in  the  blood  of  the  heart;  hemolytic  streptococci  and  B.  influenza?  in  the 
lung. 

.Microscopic  examination  shows  that  the  walls  of  the  bronchi  are  in- 
filtrated with  lymphoid  and  plasma  cells;  these  cells  are  very  numerous 
in  peribronchiolar  patches  of  consolidation.  A  small  bronchus  1  mm.  in 
diameter  lias  squamous  epithelium  alone.-  one  side;  on  the  opposite  side,  the 
wall  is  completely  absent  and  there  is  superficial  necrosis  of  exposed  al- 
veoli tilled  with  fibrin.  A  deep  fissure  passes  from  the  bronchus  into  the 
consolidated  tissue;  its  edges  are  necrotic  and  it  is  filled  with  polynuclear 
leucocytes.  A  small  cavity  in  contact  with  the  bronchus  has  been  formed. 
In  another  part  of  the  lung  a  distended  bronchus  has  lost  its  epithelium 
on  one  side,  and  here  alveoli  filled  with  fibrin  form  the  wall  of  the  bronchus 
which  is  tilled  with  leucocytes.  Extending  outward  from  the  eroded  wall 
is  a  focus  of  necrosis  where  both  alveolar  walls  and  contained  exudate 
have  lost  their  nuclei. 

The  necrosis  which  lias  had  its  origin  in  the  bronchi  is 
soon  followed  by  accumulation  of  polynuclear  leucocytes, 
softening  and  disintegration  of  tissue.  Discharge  of  the 
disintegrated  tissue  through  the  bronchi  results  in  the  for- 
mation of  a  small  cavity  continuous  with  the  bronchus. 
These  changes  are  well  illustrated  by  the  bronchogenic 
abscesses  which  have  been  described  elsewhere  (Autopsies 
376,  p.  206,  and  387,  p.  206).     When  disintegrated  tissue 


PATHOLOGY  AND  BACTEKIOLOG'Y    FOLLOWING    I  X  FL1 '  KXZA     257 

is  discharged  by  way  of  the  bronchi  no  accumulation  of  pus 
occurs,  but  cavities  will  be  formed,  in  part  by  dilation  of 
bronchi,  in  part  by  erosion  of  the  adjacent  lung  tissue.  His- 
tologic examination  shows  that  these  changes  have  pro- 
duced the  advanced  bronchiectasis  found  in  Autopsy  445 
(Fig.  25). 

Autopsy  445. — W.  F.,  white,  aged  twenty-three,  from  Mississippi,  had  been 
in  military  service  one  month.  His  illness  began  September  22,  twenty- 
seven  days  before  death,  with  severe  coryza,  weakness,  nausea  and  vomit- 
ing; great  pain  in  bones,  cough  and  sore  throat.  He  was  admitted  to  the 
base  hospital  one  week  later  with  diagnosis  of  influenza  and  bronchitis. 
On  October  3,  sixteen  days  before  death,  signs  of  consolidation  were  found 
on  the  left  side  over  the  back  and  a  diagnosis  of  lobar  pneumonia  was 
made.  On  October  IS  there  was  severe  headache,  pupils  were  dilated,  and 
there  was  rigidity  of  neck;  lumbar  puncture  was  made  and  pneumococci 
were  found  in  the  fluid  obtained.     Death  occurred  on  the  following  day. 

Anatomic  Diagnosis. — Bronchiectasis  with  unresolved  pneumonia  limited 
to  the  left  lower  lobe;  acute  bronchopneumonia  with  peribronchiolar  con- 
solidation in  right  lung;  purulent  bronchitis,  peribronchial  hemorrhage 
and  organizing  bronchiolitis  in  right  lung;  adherent  pleura  on  left  side; 
purulent  meningitis. 

The  left  upper  lobe  is  crepitant  throughout.  The  outer  and  posterior 
two-thirds  of  the  left  lower  lobe  is  riddled  with  cavities  often  rounded 
and  varying  in  diameter  from  0.5  to  3  cm.  but  not  infrequently  irregular 
in  shape  and  in  communication  with  adjacent  cavities  (Fig.  25).  In  places 
cavities  pass  in  a  tortuous  course  from  pleura  to  the  midpart  of  lung. 
The  lining  of  these  cavities  is  usually  smooth,  but  in  places  is  covered 
by  gray  necrotic  material.  Communication  between  the  cavities  and  me- 
dium-sized bronchi  is  occasionally  found.  The  lung  tissue  between  the 
cavities  is  in  part  grayish  red  and  consolidated,  in  part  pink  and  air  con- 
taining. The  right  lung  is  edematous  throughout ;  the  bronchi  in  the  lower 
part  of  the  right  lung  contain  purulent  fluid  and  are  in  places  surrounded 
by  zones  of  hemorrhage. 

The  spleen  is  very  large  (14  x  11  x  5  cm.)   and  firm. 

The  spinal  fluid  is  cloudy  and  blood  vessels  over  the  lumbar  enlargement 
and  lower  thoracic  region  are  congested;  in  the  upper  thoracic  region  the 
cord  is  covered  by  purulent  exudate. 

Bacteriologic  examination  demonstrates  the  presence  of  hemolytic  strep- 
tococci in  the  blood  of  the  heart;  plates  from  the  left  lung  contain  a  few 
colonies  of  S.  aureus  and  Pneumococcus  IV;  plates  from  the  right  main 
bronchus  contain  S.  aureus  and  a  large  bacillus  which  does  not  stain  by 
Gram's  method.  Three  plates  from  the  spinal  meninges  contain  Pneu- 
mococcus  IV. 

Microscopic  examination  shows  that  the  cavities  which  have  been  de- 
scribed are  lined  by  very  vascular   connective   tissue   containing  many   cells; 


258      PNEUMONIAS  A.ND   INFECTIONS  OF   RESPIRATOR?   TRACT 


Fig.    25.— Advanced   bronchiectasis    throughout   lower   left   lobe.     Autopsy    AAb 


PATHOLOGY  AND  BACTERIOLOGY    FOLLOWING    [NFLUENZA     259 

there  is  no  epithelial  lining  and  the  surface  is  in  places  covered  by  fibrin. 
On  the  surface  poly-nuclear  leucocytes  are  numerous,  bu1  immediately  be 
low,  large  mononuclear  cells  occur  and  frequently  contain  one  or  several 
ingested  polynuclear  leucocytes.  None  of  the  structures  peculiar  to  the 
bronchi  can  be  identified  in  the  wall  of  these  cavities,  and  in  many  places 
it  is  evident  that  lung  tissue  lias  undergone  destruction,  for  in  places  the 
lining  of  vascular  connective  tissue  is  interrupted  and  an  extension  of  the 
cavity  penetrating  into  the  lung  substance  is  surrounded  by  alveoli  filled  with 
fibrin;  in  contact  with  the  cavity  there  is  some  necrosis. 

The  cavities  communicate  with  the  bronchi  and  are 
lined  in  part  by  vascular  connective  tissue  which  may  in 
part  represent  preexisting  bronchial  walls,  but  no  epithe- 
lium is  present  and  the  relation  to  the  bronchi  cannot  be  es- 
tablished with  certainty.  These  cavities  have  extended  by 
necrosis  which  has  broken  the  vascular  connective  tissue  of 
their  wall  and  penetrated  into  adjacent  lung  tissue.  Death 
has  been  the  result  of  purulent  meningitis  caused  by  pneu- 
mococcus,  and  the  histologic  changes  in  the  walls  of  the 
cavities  suggest  that  the  activity  of  the  inflammatory  reac- 
tion here  is  subsiding,  for  large  mononuclear  cells  are  nu- 
merous and  are  ingesting  polynuclear  leucocytes.  The 
changes  described  would,  if  continued,  result  in  the  forma- 
tion of  cavities  lined  by  fibrous  tissue  and  resembling  many 
of  those  formed  as  the  result  of  dilatation  of  the  bronchi. 

A  study  of  the  progress  of  the  changes  which  result  in 
the  formation  of  bronchiectatic  cavities  has  shown  how  the 
inflammatory  irritant  within  the  bronchus  destroys  the  epi- 
thelium of  the  bronchus,  penetrates  into  the  deeper  tissues 
and  produces  fissures  which  extend  through  the  entire 
thickness  of  the  bronchial  wall  at  one  or  usually  several 
places.  These  longitudinal  fissures,  which  at  first  often 
give  a  stellate  outline  in  cross  section  to  the  cavity  of  the 
affected  bronchus,  permit  the  separation  of  the  edges  of  the 
fissure,  so  that  an  increase  in  the  circumference  occurs. 
The  base  of  the  fissure  is  formed  by  surrounding  alveolar 
tissue  and  its  edges  are  the  site  of  necrosis.  Tears  may 
extend  into  the  surrounding  alveolar  tissue,  thus  permit- 
ting further  stretching  of  the  bronchial  wall.     The  conse- 


260      PNEUMONIAS  AND   [NFECTIONS  OF  RESPntATOIfX  TRACT 

quences  of  rupture  of  the  small  bronchi  into  the  adjacent 
alveoli  are  to  some  extent  overcome  by  the  inflammatory 
reaction  which  plugs  the  adjacent  alveoli  with  fibrin. 

Compression  of  the  lungs  by  forced  expiration,  even 
though  the  glottis  were  closed  as  in  coughing,  would  not 
dilate  the  bronchi,  because  pressure  outside  and  within  the 
bronchi  would  be  equally  elevated  (Thornton  and  Pratt0). 
The  pressure  within  the  bronchi  does  not  differ  greatly 
from  atmospheric  pressure,  whereas  the  negative  pressure 
within  the  pleural  cavity  may  vary  from  approximately 
6  mm.  of  mercury  during  quiet  inspiration  to  30  mm.  with 
forced  inspiration.  Excess  of  pressure  upon  the  inner  sur- 
face of  the  bronchial  walls  will  vary  with  coughing  and 
other  respiratory  efforts,  between  these  limits  depending 
upon  the  readiness  with  which  pressure  is  equalized  within 
and  without  the  bronchi  by  penetration  of  air  into  the  alve- 
oli. The  presence  of  viscid  mucopurulent  fluid  within  bron- 
chioles will  obstruct  these  tubules  and  retard  the  entrance 
of  air  into  alveoli. 

Weakening  of  the  bronchial  wall  by  the  changes  which 
have  been  described  will  cause  lasting  dilatation  of  the 
bronchi.  Whatever  increases  pressure  within  the  bronchi 
will  increase  the  tendency  to  dilatation;  the  bronchi  being 
filled  with  mucopurulent  exudate  dilatation  usually  ap- 
pears first  at  the  bases  of  the  lung,  since  gravity  increases 
intrabronchial  pressure  here.  New7  formation  of  fibrous 
tissue  within  the  wall  of  the  bronchus,  thickening  of  adja- 
cent alveolar  walls,  and  organization  of  fibrin  reinforce  the 
weakened  bronchial  wall  and  limit  the  dilatation  which  fol- 
lows injury  to  the  wall.  "Regeneration  of  epithelium  cov- 
ering the  dilated  tube  will  further  obscure  the  early 
changes  which  have  made  dilatation  possible.  The  changes 
which  weaken  the  bronchial  wall  permit  dilatation  at  a 
time  when  there  is  no  new  formation  of  fibrous  tissue. 
When  the  bronchial  lesion  has  persisted    several    weeks, 

•Thornton  and   Pratt:   Hull.  Johns  Hopkins   Hosp.,  1908,   xix,  230. 


PATHOLOGY  AND  BACTERIOLOGY    KOLLOWIXC    IXI'U'KXZA     'K\\ 

chronic  pneumonia  is  associated  with  it.  It  has  been  sug- 
gested that  the  contraction  of  newly  formed  fibrous  1  issue 
within  the  substance  of  the  lung  might  cause  bronchi  to  be 
enlarged  by  traction  upon  their  walls.  Newly  formed  con- 
nective tissue  is  most  abundant  in  the  wall  of  the  bronchi- 
ectatic  cavity,  and  here  contraction  would  tend  to  diminish 
the  size  of  the  cavity. 

Unresolved  Bronchopneumonia 

Chronic  bronchopneumonia  is  characterized  by  changes 
similar  to  those  associated  with  chronic  inflammation  in 
other  parts  of  the  body,  namely,  by  thickening  of  the  inter- 
stitial tissue  of  the  lung,  by  accumulation  of  mononuclear 
cells,  by  proliferation  of  fibrous  tissue  and  by  organization 
of  exuded  fibrin.  In  a  few  instances  these  changes  have  be- 
gun at  the  end  of  two  weeks  after  onset  of  influenza,  but 
they  have  been  little  advanced  until  three  weeks  has 
elapsed ;  advanced  chronic  inflammation  has  occurred  after 
from  four  to  eight  weeks.  Chronic  inflammation  primarily 
affects  those  structures  which  are  most  severely  injured  by 
the  acute  lesion  and  is  most  conspicuous  in  immediate  prox- 
imity to  the  small  bronchi  and  bronchioles;  the  perivascu- 
lar and  interlobular  connective  tissue  are  secondarily 
involved.  Corresponding  to  each  of  the  lesions  of  the  alve- 
olar tissue  which,  have  been  found  with  bronchopneumonia, 
namely,  peribronchiolar,  hemorrhagic  peribronchiolar,  lob- 
ular and  peribronchial  consolidation,  there  is  a  chronic  le- 
sion which  develops  when  pneumonia  has  failed  to  resolve. 

The  term  interstitial  bronchopneumonia  has  been  used 
by  MacCallum  to  designate  a  lesion  which  he  has  found  in 
association  with  measles  at  Fort  Sam  Houston.  This  name 
he  states  does  not  describe  accurately  the  early  stage  of  the 
lesion,  for  its  interstitial  character  is  not  evident  at  first.  In 
his  monograph  on  ''Epidemic  Pneumonia  in  the  Army 
Camp,"  published  in  1919,  MacCallum  describes  and  pic- 


_!>_      PNEUMONIAS   AND   INFECTIONS  OF   RESPIRATOR'S   TRACT 

twees  instances  of  the  lesion  which  we  have  designated  in- 
terstitial suppurative  pneumonia  and  classifies  them  as  in- 
terstitial bronchopneumonia.  We  have  shown  thai  this  Le- 
sion, which  is  the  result  of  infection  of  the  Lymphatics  with 
S.  hemolyticus,  hoars  no  necessary  relation  to  the  lesion 
which  is  characterized  in  its  early  stage  by  peribronchiolar 
pneumonia  and  in  its  later  stages  by  chronic  inflammation 
with  mononuclear  infiltration  and  proliferation  of  the  peri- 
bronchial, perivascular  and  interalveolar  tissue.  At  Fort 
Sam  Houston,  nearly  every  patient  with  measles  was  in- 
fected with  hemolytic  streptococci;  we  observed,  following 
influenza,  similar  prevalence  of  hemolytic  streptococci  in 
certain  wards  in  the  base  hospital  at  Cam])  Pike.  Among  the 
cases  at  Fort  Sam  Houston  there  were  doubtless  instances 
both  of  interstitial  suppurative  pneumonia  caused  by  hemo- 
lytic streptococcus  and  of  chronic  bronchopneumonia  not 
referable  to  this  microorganism. 

Studying  pneumonia  following  influenza  at  Camp  Lee, 
A'a.,  and  later  at  Camp  Dix,  X.  J.,  during  the  fall  of  1918, 
MacCallum  reached  the  conclusion  that  "interstitial  bron- 
chopneumonia" following  influenza  was  caused  by  B.  influ- 
enzae of  Pfeiffer.  This  lesion  attributed  to  B.  influenzae 
differed  from  that  previously  referred  to  hemolytic  strep- 
tococcus in  the  following  characters:  the  lymphatic  chan- 
nels in  the  bronchial  walls  and  widened  interlobular  septa 
are  inconspicuous  and  none  are  found  distended  with  exu- 
date ;  there  is  no  intense  infection  of  the  pleura,  and  poly- 
nuclear  leucocytes  are  inconspicuous  in  the  alveolar  exu- 
date and  in  the  wTalls  of  the  bronchi.  It  seems  probable 
these  differences  are  explained  by  the  absence  of  hemolytic 
streptococci  which  tend  to  invade  lymphatics  and  produce 
severe  inflammatory  changes  in  the  pleura. 

Chronic  Bronchitis.  The  earliest  changes  in  the  bron- 
chial wall  with  bronchitis  of  influenza  are  hyperemia,  leu- 
cocytic  infiltration  and  hemorrhage,  and  they  may  occur 
even  though  the  lining  epithelium  remains  intact.    Epithe- 


PATHOLOGY  AND  BACTEBIOLOGY  FOLLOWING    IXFU'KXZA     263 

lium  frequently  undergoes  partial  or  complole  dcsl  i-iu-tion, 
and  with  this  severe  injury  the  influence  of  the  Lnflanraia 
tory  irritant  may  extend  directly  through  the  wall  of  the 
bronchus,  for  in  some  instances  there  is  hemorrhage  into 
all  the  alveoli  in  a  zone  encircling  the  bronchus.  Since  these 
alveoli  have  only  indirect  communication  with  the  affected 
bronchus  through  alveolar  tissue  not  involved  in  the  in- 
flammatory process,  it  is  evident  that  the  surrounding 
hemorrhage  is  secondary  to  the  lesion  of  the  bronchus. 
Fibrinous  inflammation  in  other  instances,  similarly  local- 
ized in  a  zone  of  alveoli  encircling  a  bronchus,  is  doubtless 
the  result  of  direct  extension  of  the  inflammatory  process 
through  the  bronchial  wall.  After  the  disease  has  existed 
during  two  or  three  weeks  inflammation  is  still  active  im- 
mediately below  the  inner  surface  of  the  bronchus;  here 
polynuclear  leucocytes  are  numerous  whereas  in  the  deeper 
parts  of  the  mucosa  and  about  the  muscularis  leucocytes  are 
scant  but  lymphoid  and  plasma  cells  are  very  numerous. 
The  severity  of  the  inflammatory  reaction  may  be  judged 
by  the  abundance  and  extent  of  this  cellular  reaction  and  is 
in  close  relation  to  the  intensity  of  the  changes  affecting 
the  mucous  membrane  of  the  bronchus.  Infiltration  of  the 
entire  bronchial  wall  with  lymphoid  and  plasma  cells  is 
almost  invariable  when  the  primary  injury  to  the  bronchus 
has  destroyed  the  epithelial  lining,  and  this  infiltration  is 
not  limited  to  the  bronchial  wall  but  extends  outward  into 
the  contiguous  alveolar  septa  which  are  thickened  by  it. 
The  sheath  of  the  pulmonary  artery  which  accompanies  the 
bronchus  exhibits  a  similar  change,  and  the  alveolar  septa, 
as  a  fringe  about  it,  are  thickened  and  infiltrated  with  mon- 
onuclear cells.  Interlobular  septa  continuous  with  the  bron- 
chus often  show  some  infiltration. 

A  later  phase  in  this  series  of  changes  is  represented  bv 
new  formation  of  fibrous  tissue.  The  bronchial  walls  and 
interalveolar  septa  are  thickened  by  proliferating  fibrous 
tissue,  young  fibroblasts  and  newly  formed  collagen  fibrils 


264      PNEUMONIAS  AND   [NFECTIONS  OF  RESPIRATOR'S  TRACT 

being  abundant  (Fig.  iN:  also  Fig.  ."lit).  This  increase  of 
fibrous  tissue  is  especially  noteworthy  immediately  sur- 
rounding the  walls  of  the  small  bronchi,  which  are  often 
considerably  dilated,  and  aboul  the  smaller  of  those  bron- 
chi which  have  cartilage;  with  thickening  of  alveolar  walls 
immediately  adjacent  to  the  bronchus  every  stage  in  the 
obliteration  of  the  alveoli  may  he  found.  Their  walls  are 
thickened  and  their  lamina  are  diminished  in  size  and  often 
flattened  in  a  direction  concentric  with  the  bronchus.  Such 
atrophied  alveoli  lined  by  cubical  epithelial  cells  occurring 
within  the  thickened  peribronchial  fibrous  tissue  give  evi- 
dence that  this  tissue  has  replaced  alveoli.  Alveoli  sur- 
rounding and  within  the  new  fibrous  tissue  are  fre- 
quently tilled  with  fibrin,  and  organization  indicated  by 
penetration  of  fibroblasts  and  capillaries  into  the  fibrin 
may  he  far  advanced.  There  is  some  increase  of  perivascu- 
lar and  interlobular  tissue.  The  bronchiectasis  which  is 
almost  invariably  found  with  unresolved  bronchopneumo- 
nia has  been  described.  Squamous  transformation  of  epi- 
thelium (page  251)  is  frequently  found  in  association  with 
the  chronic  bronchitis  of  unresolved  pneumonia. 

Organizing  Bronchitis  and  Bronchiolitis. — When  the 
bronchial  epithelium  is  destroyed,  fibrin  is  deposited  upon 
the  denuded  surface  and  may  partly  or  completely  fill  the 
lumen  of  the  bronchial  tube.  The  plug  of  fibrin  is  adherent 
to  the  underlying  tissue  wherever  epithelium  is  lost  hut  is 
separated  from  the  bronchial  wall  by  a  well-defined  space 
where  epithelial  lining  is  still  intact.  Fibroblasts  promptly 
migrate  Prom  the  wall  of  the  bronchiole  into  this  fibrin,  and 
fibroblasts,  fixed  during  ameboid  movement,  are  irregularly 
elongated  in  a  direction  toward  the  fibrin. 

Organization  of  fibrin  occurs  within  the  smallest  bronchi 
(diameter  0.3  to  0.5  mm.)  or  within  respiratory  bronchioles. 
It  lias  been  found  in  8  autopsies.  In  one  instance  it  has 
been  present  eleven  days  after  the  onset  of  influenza,  hut 
usually  it  is  seen  three  or  four  weeks  after  onset  of  symp- 


PATHOLOGY  AND   BACTERIOLOGY    FOLLOWING    I  X  FL1 '  KXZA     265 

toms  of  respiratory  disease.  In  the  early  stages  of  the 
lesion  a  plug  of  fibrin  within  the  lumen  of  the  bronchus  or 
bronchiole  is.  invaded  by  fibroblasts,  plasma  cells  and  newly 
formed  capillaries.  These  capillaries  have  their  origin  in 
the  wall  of  the  tube  and  enter  the  fibrin  at  points  where 
in  consequence  of  loss  of  epithelium  fibrin  is  continuous 
with  the  connective  tissue.  When  the  bronchiole  is  cut 
longitudinally,  partially  or  completely  organized  fibrin  may 
be  found  adherent  at  several  places  with  intact  epithelium, 
sometimes  beautifully  ciliated,  between  the  sites  of  attach- 
ment. The  fibrin  is  finally  replaced  completely  and  the 
lumen  of  the  bronchiole  contains  a  mass  of  organized 
fibrous  tissue  in  which  young  fibroblasts  and  plasma  cells 
are  numerous. 

The  lesion  has  been  associated  with  chronic  bronchopneu- 
monia in  6  of  8  instances.  In  Autopsy  445,  p.  257,  organ- 
izing bronchitis  and  bronchiolitis  occurred  in  the  right  lung 
unassociated  with  other  chronic  lesion,  although  there  was 
advanced  bronchiectasis  with  fibrous  induration  in  the 
left  lung.  In  Autopsy  499  (p.  224)  organizing  bronchiolitis 
occurred  in  association  with  chronic  changes  which  appear 
to  have  followed  interstitial  suppurative  pneumonia  caused 
by  S.  hemolyticus.  Other  severe  lesions  of  the  bronchi 
have  accompanied  organizing  bronchitis  and  bronchiolitis. 
Purulent  bronchitis  has  been  present  in  7  of  8  instances; 
bronchiectasis  in  5  of  8  instances. 

The  bacteriology  of  autopsies  with  organizing  bronchitis 
and  bronchiolitis  is  shown  in  Table  LIII. 

The  bacteriology  of  these  cases  presents  no  constant 
feature.  Invasion  of  the  blood  by  S.  hemolyticus  has  been 
present  in  a  large  proportion  of  cultures,  namely,  in  5  of  7 
(71.4  per  cent).  In  one  of  the  2  instances  in  which  hemo- 
lytic streptococci  have  been  found,  neither  in  the  blood  nor 
lungs,  Pneumococcus  III  has  been  found  in  the  blood  and  S. 
viridans  in  the  lungs  and  bronchus ;  in  the  other,  S.  aureus 
has  been  found  in  the  lung  and  bronchus.     Staphylococci 


266      PNEUMONIAS    \\l>   INFECTIONS  OF   RESPIRATOR'S   TRACT 

TAB]  E    I.I  I  I 


AlTdl'SV 

Dl  RAMON 
OF  ILLNESS 

BLOOD 

I  CJNGS 

BRONCHI  S 

4L'0 

11     days 

S.  hem. 

s.  hem.,  B.  inf..  8 

102 

14       " 

Pneum.    I V,  S. 

aur. 

370 

457 

ll'l 

17       " 

17+     " 
19       " 

hem. 
s.   hem. 

s.   aur. 
Pneum.  IV,  s. 

S.   aur.,  Pneum. 

IV.  B.  inf. 
Pneum.  IV,  11.  inf. 

445 

27       " 

S.   hem. 

hem. 
Pneum.    IV,   S. 
aur. 

S.  aur. 

473 

499 

28+     " 
36       " 

Pneum.    1 1  r 
S.   horn. 

S.  vir. 

B.  inf.,  S.  vir., 

staph.,  M. 

catarr. 
S.    hem.    B.    inf. 

have  been  round  frequently  in  the  bronchi  (60  per  cent) 
and  in  the  hmgs  (50  per  cent).  B.  influenzae  lias  been  pres- 
ent in  the  bronchi  in  the  usual  proportion  of  instances 
(80  per  cent).  The  lesion  lias  occurred  in  the  presence  of 
15.  influenzas  combined  with  streptococci  or  staphylococci. 

Thrombosis  of  lymphatics  in  the  Avail  of  bronchi  adjacent 
to  blood  vessels  and  in  interlobular  septa  occurs,  and  occa- 
sionally organization  of  the  fibrinous  plug  within  the  lym- 
phatic is  in  progress  (Autopsies  2S3,  425  and  463).  Fibro- 
blasts and  capillaries  penetrate  from  the  wall  of  the  lym- 
phatic into  a  mass  of  hyaline  fibrin  which  fills  the  lumen. 

Unresolved  Bronchopneumonia. — The  most  common  type 
of  pneumonic  lesion  following  influenza  is  characterized  by 
acute  inflammation  of  the  alveoli  immediately  adjacent  to 
the  bronchioles  and  the  lesion  is  associated  in  many  in- 
stances with  hemorrhage  or  edema.  If  this  lesion  persists 
unresolved  during  several  weeks,  evidences  of  chronic  in- 
flammation are  found.  Peribronchial,  perivascular  and  in- 
terlobular connective  tissue  is  thickened  and  richly  infil- 
trated with  lymphoid  and  plasma  cells,  large  mononuclear 
cells  and  many  young  fibroblasts.  Interalveolar  septa  ad- 
jacent to  the  walls  of  bronchi  and  between  alveoli  surround- 
ing inflamed  bronchioles  are    implicated    in    the    process. 


PATHOLOGY  AND  BACTERIOLOGY   FOLLOWING    I  NTL1 '  B  X  ZA     267 

Interstitial  changes  characterize  the  lesion  only  in  its  late 
stage.  It  appears  undesirable  to  give  the  name  "interstitial 
pneumonia"  to  the  early  stage  of  a  lesion  which  begins  and 
in  most  instances  terminates  as  an  acute  relatively  super- 
ficial inflammation  of  the  bronchi,  bronchioles  and  peri- 
bronchiolar alveoli. 

Chronic  bronchopneumonia  is  often  overlooked  at  au- 
topsy because  newly  formed  connective  tissue  is  not  present 
in  sufficient  quantity  to  attract  attention  (Fig.  26).  When 
the  lesion  is  advanced  conspicuous  gray  white  patches  of 
fibrous  tissue  may  be  seen  about  the  bronchi  (Autopsy  487; 
Fig.  27)  and  interlobular  septa  may  be  obviously  thickened 
(Autopsy  472).  The  most  distinctive  feature  of  the  lungs 
is  the  presence  of  small,  firm,  gray  or  yellowish  gray  nod- 
ules of  consolidation  which  resemble  miliary  tubercles. 
They  represent  the  peribronchiolar  patches  of  broncho- 
pneumonia present  during  the  acute  stage  and  have 
assumed  the  well-defined  outline  and  firm  consistence  of 
tubercles  because  polynuclear  leucocytes  and  red  blood  cor- 
puscles have  in  large  part  disappeared,  interstitial  tissue 
is  increased,  and  exudate  is  in  process  of  organization. 
These  nodules  are  grouped  in  clusters  about  the  small 
bronchi. 

With  unresolved  bronchopneumonia  the  lungs  are  very 
voluminous  and  fail  to  collapse  after  they  are  removed  from 
the  chest  and  in  some  instances  even  after  incision.  The 
air  containing  tissue  is  usually  dry.  In  our  autopsies  the 
lungs  have  been  pink  in  color  and  often  free  from  coal  pig- 
ment, because  those  suffering  with  pneumonia  have  been  in 
considerable  part  men  from  rural  districts.  Thick  muco- 
purulent material  exudes  from  the  small  bronchi  which 
have  been  cut  across ;  purulent  bronchitis  has  been  present 
in  20  of  21  instances  of  chronic  bronchopneumonia.  Bron- 
chiectasis has  been  present  in  13  instances;  dilatation  is 
often  advanced,  so  that  throughout  the  lungs  are  found 
bronchi  with  no  cartilage  distended  to  a  diameter  of  0.5  cm. 


268      PNEUMONIAS   A.ND   [NFECTIONS  OF   RESPIRATORY  TRACT 


I'ig.    26, 


-Unresolved     bronchopneumonia     with     tubercle-like     nodules     of    peribronchiolar 
consolidation  best   seen   in   lower   lobe;   bronchiectasis.     Autopsy   425. 


PATHOLOGY  A  X  I )  I  iA  ( !TE  RIOLOGY   FOLLOWING   [NFLUE  N  ZA       269 

In  addition  to  the  firm  peribronchiolar  tubercle-like  nod- 
ules of  consolidation  there  are  scattered  patches  of  gray 
lobular  or  confluent  lobular  consolidation.  Yellowish  nod- 
ules, grouped  about  bronchi  and  resembling  those  found 
elsewhere  in  air  containing  tissue,  are  occasionally  seen 
scattered  upon  the  cut  surface  of  a  patch  of  gray,  confluenl 
lobular  consolidation  (Autopsies  421,  423,  431). 

Microscopic  examination  demonstrates  the  presence  of 
those  changes  which  have  been  described  in  association 
with  chronic  bronchitis  and  bronchiectasis.  There  is  abun- 
dant new  formation  of  fibrous  tissue  about  the  bronchi  of 
small  and  medium  size,  thickening  of  adjacent  interalveolar 
walls  and  incorporation  of  alveoli  into  the  thickened  bron- 
chial wall  (Figs.  27,  28,  30,  and  31).  In  half  of  the  in- 
stances of  chronic  bronchopneumonia  there  has  been  peri- 
bronchial fibrinous  pneumonia,  and  organization  of  fibrin 
within  the  alveoli  is  usually  well  advanced.  In  one  instance 
(Autopsy  487;  Figs.  27  and  28)  after  an  illness  of  fifty-five 
days  this  process  has  resulted  in  the  formation  of  conspic- 
uous patches  of  firm,  grayish  white  fibrous  tissue  surround- 
ing dilated  bronchi.  Organization  of  fibrinous  exudate 
within  the  lung  has  not  been  limited  to  the  alveoli  but  has 
occurred  in  the  bronchioles  as  well.  Organizing  bronchio- 
litis has  been  present  in  5  instances  (Autopsies  370,  402, 
457  and  473). 

Increase  of  fibrous  tissue  occurs  about  the  blood  vessels 
and  in  the  septa  between  the  lobules,  which  are  infiltrated 
with  mononuclear  wandering  cells  and  fibroblasts.  Dila- 
tation and  thrombosis  of  the  lymphatic  vessels  have  oc- 
curred in  both  situations,  and  in  3  instances  (Autopsies 
283,  425  and  463)  organization  of  these  fibrinous  thrombi 
has  occurred. 

Thickening,  cellular  infiltration  and  fibrosis  of  the  bron- 
chial walls  with  interstitial  inflammation  and  fibrosis  of  im- 
mediately adjacent  alveolar  septa  are  found  about  the 
ramifications  of  the  bronchial  tree  and  may  be  followed 


270      PNEUMONIAS  AND   INFECTIONS  OF   RESPIRATORS   TRACT 


Irig.    27. —  Unresolved    pneumonia    with    peribronchial    formation    of    fibrous    tissue;    bron- 
chiectasis.    Autopsy    487. 


PATHOLOGY  AND   BACTERIOLOGY    FOLLOWING    I  X  FIJ'KXXA     271 

to  the  smallest  bronchi.  When  the  respiratory  bronchioles 
are  readied  it  will  be  found  that  the  alveoli  which  stud  1  heir 
walls  are  implicated  in  the  change.  The  fibrin  which  they 
contain  is  infiltrated  with  lymphoid  and  plasma  cells,  and 
with  progress  of  the  lesion  is  invaded  by  fibroblasts  and 
capillaries.  Infiltration  and  fibroid  thickening  extends 
from  the  bronchiolar  wall  to  the  alveolar  septa  continuous 
with  it  (Fig.  31  with  measles).  Similar  changes  occur  aboul 


s%**  ■> 

*$if* 

Fig.  28. — Unresolved  pneumonia  with  bronchiectasis  showing  new  formation  of  fibrous 
tissue  about  a  greatly  dilated  bronchus  of  which  the  epithelial  lining  has  been  lost. 
Autopsy  487. 


the  alveolar  ducts,  and  about  the  orifices  of  the  tributary 
infundibula  (Fig.  32),  peribronchiolar  foci  of  acute  inflam- 
mation having  assumed  the  characters  of  a  chronic  inflam- 
matory process.  Fibrin  within  the  alveoli  contains  round 
cells  and  fibroblasts.  With  thickening  of  alveolar  walls  the 
alveolar  lumina  may  be  much  diminished  in  size  and  often 
persist  as  spaces  lined  by  cubical  cells.  Polynuelear  leu- 
cocytes are  usually  numerous  within  the  alveolar  duct  and 


Li_      PNEUMONIAS  AND   [NFECTIONS  OF  RESPIRATOR?  TRACT 

in  a  few  alveoli  immediately  adjacent  to  it,  but  elsewhere 
throughoul  the  focus  of  inflammation  round  cells  arc  pre- 
dominant. The  changes  which  have  been  described  corre- 
spond with  the  transformation  of  ill-defined,  gray  or  red- 
dish gray  spots  of  consolidation  grouped  about  the  termi- 
nal bronchi  into  firm  sharply  denned  grayish  while  nodules 
having  the  consistence  and  appearance  of  miliary  tubercles. 
One  of  the  most  constant  characters  of  pneumonia  fol- 
lowing influenza  is  its  hemorrhagic  character.  In  the 
earlier  stages  of  pneumonia  phagocytosis  of  red  blood  cor- 
puscles by  large  mononuclear  cells  is  frequently  seem.  In 
association  with  the  chronic  changes  which  have  been  de- 
scribed, large  mononuclear  cells  filled  with  brown  pigment, 
doubtless  formed  from  red  corpuscles,  are  often  found 
within  the  alveoli.  These  pigment  containing  cells  are  sim- 
ilar to  those  commonly  associated  with  chronic  passive  con- 
gestion of  the  lungs. 

In  one  instance  (Autopsy  457)  hemorrhagic  peribron- 
chiolar pneumonia  has  been  found  in  process  of  organiza- 
tion. The  bronchioles  and  alveoli  adjacent  to  them  contain 
polynuclear  leucocytes,  but  intervening  alveoli  almost  uni- 
formly contain  blood  and  are  the  site  of  new  formation  of 
connective  tissue.  Interalveolar  septa  are  thickened  and 
alveoli  which  arc  lined  by  cubical  epithelium  are  often  di- 
minished in  size.  In  many  places  fibroblasts  have  pene- 
trated in  considerable  number  into  the  blood  within  the  al- 
veoli and  occasionally  newly  formed  capillaries  are  found 
within  them. 

Lobular  patches  of  pneumonia  are  often  found  in  process 
of  organization  (Autopsies  370,  421,  42:5,  433,  463,  472  and 
473).  Microscopic  examination  shows  that  whole  lobules 
well  defined  by  thickened  septa  are  the  site  of  chronic  in- 
teralveolar inflammation  and  intraalveolar  organization  of 
exudate,  whereas  adjacent  lobules  are  air  containing  and 
relatively  normal.  In  the  earlier  stages  of  the  process 
fibrin  present   within  the  alveoli  is  invaded  by  fibroblasts, 


PATHOLOGY  AND   BACTERIOLOGY    FOLLOWING    INFLUENZA     273 

mononuclear  wandering  cells  and  Mood  vessels  bill  in  tlie 
later  stages  fibrin  lias  disappeared;  the  lumina  of  the  alve- 
oli are  occupied  by  cellular  fibrous  tissue  and  in  places  the 
thickened  alveolar  Avails  and  intraalveolar  fibrous  tissue 
have  been  fused  to  form  wide  patches  of  new  tissue. 

With  chronic  bronchopneumonia  confluent  lobular  con- 
solidation occasionally  has  a  gray  ground  upon  which  are 
scattered  small  yellow  spots  clustered  about  the  small 
bronchi  (Autopsies  421,  423  and  431).  Microscopic  exam- 
ination has  shown  that  the  yellowish  spots  correspond  to 
dilated  bronchioles  filled  with  purulent  exudate  and  sur- 
rounded with  alveoli  containing  many  polynuclear  leuco- 
cytes. In  the  interstitial  tissue  about  the  bronchiole  and 
between  adjacent  alveoli  plasma  cells  are  often  present  in 
great  number.  Between  these  spots  of  subacute  bronchio- 
lar  inflammation  lung  tissue  is  the  site  of  interalveolar  pro- 
liferation of  fibrous  tissue  and  intraalveolar  organization  of 
exudate. 

In  all  instances  of  chronic  bronchopneumonia  there  has 
been  peribronchial  pneumonia  in  a  zone  encircling  small 
bronchi  with  no  cartilage  and  the  smallest  of  the  bronchi 
which  have  cartilage  in  their  wall;  thickening  of  interal- 
veolar septa,  organization  of  peribronchial  fibrinous  pneu- 
monia and  partial  disappearance  of  alveoli  have  been  de- 
scribed. In  the  following  autopsy  peribronchial  fibroid 
pneumonia  has  been  so  advanced  that  conspicuous  patches 
of  gray  white  tissue  surrounding  bronchi  have  replaced  in 
some  parts  of  the  lung  a  considerable  part  of  the  lung  sub- 
stance. 

Autopsy  487. — W.  C,  white,  aged  twenty-seven  years,  a  farmer  from 
Mississippi  had  been  in  military  service  twenty-one  days.  Illness  began 
on  September  17,  fifty-five  days  before  death,  with  chill,  fever,  cough,  back- 
ache, pain  in  the  chest  and  coryza.  The  patient  was  admitted  two  weeks 
after  onset  with  the  diagnosis  of  influenza.  Eight  days  later  his  sputum 
was  blood  tinged  and  there  were  signs  of  bronchopneumonia.  One  month 
after  admission  the  patient  developed  a  rash  and  a  diagnosis  of  scarlet 
fever  was  made. 


l!<4      PNEUMONIAS  AND  INFECTIONS  OF   RESPIRATOR'S  TRACT 

Anatomic  Diagnosis.— Chronic  bronchopneumonia  with  peribronchial 
fibroid  induration;  bronchiectasis;  purulenl  bronchitis;  abscesses  at  the 
bases  Qf  both  lungs;  seropurulenl   pleurisy  on  the  left  side. 

The  body,  is  much  emaciated.  The  left  pleural  cavity  contains  650 
<•.<•.  of  opaque,  'lull  yellow,  thin,  purulent  fluid.  The  surface  of  the  left 
lung  is  covered   in  spots  by  white  partially  organized   fibrin. 

On  section  of  the  right  lung  |  Pig.  27)  the  tissue  is  found  in  great  part 
air  containing  but  there  are  numerous  linn,  gray  patches,  irregular  in  shape 
and  from  1  to  _  cm.  across.  In  these  spots  the  tissue  is  tougb  and  resembles 
fibrous  tissue:  within  them  are  much  dilated  bronchi.  In  the  central  part 
of  the  upper  lobe  is  a  group  of  cavities  with  smooth  wall,  the  largest  of 
these  cavities  being  12  mm.  in  diameter;  immediately  adjacent  are  di- 
lated  bronchi.  Between  and  surrounding  these  cavities  is  gray  tissue,  like 
that  described  above.  Below  the  outer  surface  of  the  upper  lobe  is  an 
extensive  area  7  cm.  from  above  downward,  thickly  studded  with  bron- 
chiertatir  cavities,  in  the  walls  of  which  there  is  tough  fibrous  tissue. 
In  the  middle  lobe  are  several  dilated  bronchi,  the  largest  of  which  is  7  mm. 
in  diameter,  and  elsewhere  occur  dilated  bronchi  with  thickened  walls.  At 
the  base  of  the  lung  below  the  pleura  are  two  abscesses,  which  are  yellow  in 
the  center  and  surrounded  by  hemorrhagic  tissue.  At  the  posterior  part  <<\' 
the  lower  lobe  there  are  numerous  firm,  nodular,  yellowish  spots  grouped  in 
(dusters  upon  a  background  of  red,  air  containing  tissue.  The  bronchi 
throughout    the  lung  contain  mucopurulent  fluid. 

In  the  left  lung  patches  of  fibrous  tissue  are  more  numerous  than  on  the 
right  side  and  are  irregular  in  shape,  from  1  to  2  cm.  across  and  most  abun- 
dant in  the  center  of  the  upper  lobe.  This  fibrous  tissue  is  in  great  part  gray 
but  in  places  it  has  a  yellowish  tinge.  The  bronchi  everywhere  are  moderately 
dilated.     At  the  base  of  the  lung  below  the  pleura  is  an  abscess. 

The    other   organs   show   no    noteworthy    change. 

Bacteriologic  Examination. — The  fluid  in  the  left  pleura  and  right  main 
bronchus  contain  S.  hemolyticus.  B.  influenzae  is  found  in  the  right  lung  and 
right  main  bronchus. 

Microscopic  examination  shows  that  the  patches  of  dense  fibrous  tissue 
seen  at  autopsy  almost  invariably  surround  dilated  bronchi  with  no  cartilage 
in  their  walls  (Fig.  28)  and  with  a  diameter  of  from  1  to  2  or  more  milli- 
meters. These  bronchi  have  lost  their  epithelial  lining;  they'  contain  poly- 
nuclear  leucocytes,  and  their  wall  in  contact  with  the  lumen  is  infiltrated  to 
a  varying  distance  with  the  same  cells.  Their  inner  surface  is  very  irregular, 
and  superficial  necrosis  occurs.  The  limits  of  the  preexisting  bronchial  wall 
is  no  longer  recognizable  in  the  dense  surrounding  fibrous  tissue  richly  infil- 
trated with  lymphoid  and  plasma  cells.  In  contact  with  the  bronchus,  often 
in  a  wide  zone,  all  traces  of  alveoli  have  been  destroyed,  but  further  outward 
alveoli  are  represented  by  spaces  lined  by  cubical  epithelium.  At  the  peri- 
phery   of    the    zone    of    fibroid    induration    alveolar    walls    are    much    thickened 

and  richly  infiltrated  with  mononuclear  wandering  cells;  the  lumina  of  the 
alveoli  contain  plugs  of  organized  fibrous  tissue  often  covered  by  flat  or  cubical 
epithelium.     In   the  surrounding  tissue  a  few  small  bronchi  are  lined  by   col- 


PATHOLOGY  AND  BACTERIOLOGY  FOLLOWING  INFLUENZA     275 

umnar  epithelium;  there  is  scant  new  formation  of  fibrous  tissue  but  the 
alveolar  walls  are  thickened  and  infiltrated  with  cells.  Epithelium  of  the 
larger  bronchi  with  cartilage  in  their  walls  is  usually  intact  and  there  is  aboul 
them  little  peribronchial  inflammation. 

Advanced  induration  about  the  bronchioles  represents  a 
late  stage  of  chronic  peribronchiolar  pneumonia.  A  bron- 
chiole cut  transversely  is  found  in  the  center  of  a  focus  of 
induration  situated  within  relatively  normal  air  containing 
lung  tissue.  Next  the  bronchiole  which  in  some  instances 
has  wholly  or  partly  lost  its  epithelium  there  is  very  cellu- 
lar fibrous  tissue ;  further  from  the  bronchiole  alveoli  are 
much  diminished  in  size,  lined  by  flat  or  cubical  epithelium 
and  separated  by  thick  cellular  walls.  Plugs  of  cellular 
fibrous  tissue  sometimes  fill  the  alveolar  duct.  In  favorable 
sections,  cut  in  a  plane  which  shows  the  alveolar  duct  open- 
ing out  into  infundibula,  it  is  found  that  newly  formed  fi- 
brous tissue  surrounds  the  alveolar  duct  and  extends  into 
the  walls  of  its  tributary  alveoli ;  alveoli  may  be  obliterated 
by  this  fibrous  tissue.  Induration  of  alveolar  walls  is  evi- 
dent along  the  proximal  part  of  the  infundibula  which  are 
readily  demonstrable  because  they  are  much  dilated.  (See 
Fig.  32.)  The  distal  parts  of  the  infundibula  are  sur- 
rounded by  alveoli  with  delicate  walls. 

One  bronchus  retains  along  one  side  part  of  its  epithe- 
lium which  has  assumed  a  squamous  form.  In  other  places 
the  wall  has  undergone  necrosis  which  at  one  spot  extends 
deeply  into  the  surrounding  tissue.  Necrotic  tissue  in  an- 
other part  of  the  circumference  is  infiltrated  with  polynu- 
clear  leucocytes  and  separated  from  the  surrounding  tissue 
by  a  space  filled  with  leucocytes.  An  abscess  communicat- 
ing with  the  bronchus  is  thus  formed. 

The  foregoing  instance  is  an  example  of  the  chronic  fi- 
broid pneumonias  with  bronchiectasis  which  occur  as  se- 
quela? of  the  epidemic  of  influenza.  It  is  not  improbable 
that  a  considerable  number  of  those  who  suffer  with  chronic 
bronchitis  and  bronchiectasis  following  influenza  have  less 
extensive  lesions  similar  to  those  which  have  been  described. 


276      PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATOR'S  TRACT 

Bacteriology  of  Unresolved  Bronchopneumonia. — Bacte- 
ria Pound  in  the  bronchi  in  10  instances  of  chronic  broncho- 
pneumonia have  been  as  follows: 

Bacteria  i\   Bronchi  with  Chronic  Bronchopneumonia 

B.  eoli 1 

B.  influenzae  and  pneumococcus  1 

B.   influenzae  and   S.  hemolyticus   2 

B.  influenzae  and  staphylococcus  1 

s.  hemolyticus  and  B.  coli   1 

B.  influenzae,  pneumococcus  and  staphylococcus  3 

B.  influenzae,  S.  viridans  and  M.  catarrhalis  1 

Bacteria  found  in  the  lungs  in  17  instances  of  chronic 
bronchopneumonia  wore  as  follows: 

Bacteria  in  Lungs  with  Chronic  Bronchopneumonia 

B.  influenzae 1 

Staphylococcus 1 

s.   \  iridans 1 

B.  influenzae  and  pneumococcus 1 

B.  influenzae  and  S.  hemolyticus  3 

B.  influenza'  and  staphylococcus 3 

Pneumococcus  and    S.  hemolyticus 1 

s.  hemolyticus  and  B.  coli 2 

I'.,   influenza',  S.   hemolyticus  and  staphylococcus    .1 

Xo   organism   found 1 

A  noteworthy  feature  of  these  lists  is  the  multiplicity  of 
microorganism  found,  namely,  B.  influenzae,  S.  hemolyticus, 
pneumococcus,  staphylococcus,  S.  v iridans,  B.  coli,  and  M. 
catarrhalis.  More  than  one  microorganism  is  usually 
found  in  both  bronchus  and  lung.  In  the  one  instance 
(Autopsy  472)  in  which  B.  coli  alone  has  been  found  in  the 
bronchus,  B.  eoli  and  S.  hemolyticus  have  been  found  in  the 
lung  and  hemolytic  streptococcus  in  the  blood;  it  is  evident 
that  B.  coli  alone  has  not  been  responsible  for  the  lesion. 
In  one  instance  (Autopsy  487)  B.  influenza?  alone  has  been 
found  in  the  lung  but  hemolytic  streptococci  have  been 
found  in  the  bronchus,  pleura  and  blood  of  heart;  with 
S.  aureus  alone  in  the  Lung  (Autopsy  370),  S.  aureus,  Pneu- 
mococcus IV  and  B.  influenza'  have  been  found  in  the  bron- 
chus.   With  S.  viridans  alone  in  the  lung  (Autopsy  473), 


PATHOLOGY  AND   BAGTUUIOLOG Y    FOLLOWING    INFLUENZA 


(  ( 


Pneumococcus  III  has  been  found  in  the  pleura  and  in  the 
Mood  of  the  heart  and  tins  doubtless  had  an  importanl  part 
in  the  production  of  pneumonia;  S.  viridans,  M.  catarrhalis 
and  B.  influenzas  have  been  found  in  the  bronchus  in  this  in- 
stance. 

No  single  microorganism  is  associated  with  the  lesions 
but  combinations  of  B.  influenzae  with  hemolytic  strepto- 
cocci or  staphylococci  arc  common  (over  50  per  cent).  In 
Autopsy  422  B.  influenza1  and  Pneumococcus  atypical  II 
have  been  present  in  the  lungs.  Among  10  instances  in 
which  cultures  have  been  obtained  from  the  bronchus  B. 
influenza?,  is  found  8  times,  and  in  the  2  instances  in  which 
it  has  not  been  identified  B.  coli  has  been  present.  B.  in- 
fluenza? has  seldom  been  found  (Table  XXVII)  in  the  pres- 
ence of  B.  coli,  and  it  is  not  improbable  that  B.  coli  out- 
grows and  obscures  the  presence  of  B.  influenza?. 

Table  LIV  shows  the  per  cent  incidence  of  pneumo- 
cocci,  hemolytic  streptococci,  staphylococci  and  B.  in- 
fluenza? in  the  bronchus,  lung  and  heart's  blood  with  chronic 
bronchopneumonia  and  serves  as  an  index  of  the  readiness 
with  which  each  of  these  microorganisms  passes  from  bron- 
chus to  lung  and  from  lung  to  the  blood  in  this  disease. 


Table  LIV 


PNEUMOCOCCUS 
PER   CENT 
POSITIVE 

HEMOLYTIC 

STREPTOCOCCUS 

PER   CENT 

POSITIVE 

STAPHYLO- 
COCCUS 
PER  CENT 
POSITIVE 

B.  INFLUENZAE 

PER  CENT 
POSITIVE 

Bronchus 

Lung 

Blood 

40.0 

12.5 

16.6 

30.0 

56.2 
55.6 

50.0 

37.5 
0 

80.0 

68.7 

0 

Comparison  of  Table  LIV  with  the  analogous  figures 
for  acute  bronchopneumonia  shows  little  noteworthy  dif- 
ference. Pneumococci  are  less  frequently  found,  in  the 
lung  (12.5  per  cent)  and  in  the  blood  (16.6  per  cent)  with 
chronic  bronchopneumonia  than  with  acute  bronchopneu- 
monia (lung  43.9  per  cent ;  blood,  40.3  per  cent) .  Hemolytic 
streptococci  and  staphylococci  are    not    more    frequently 


278      PNEUMONIAS  A.ND   [NFECTIONS  OF   RESPIRATOR?  TRACT 

found  with  unresolved  than  with  acute  bronchopneumonia 
and  failure  to  resolve  cannol  be  referred  to  either  or  to  both 
microorganisms,  for  bronchopneumonia  nol  infrequently  re- 
mains unresolved  in  their  absence.     B.  influenzae  is  present 

in  the  bronchi  in  at  least  80  per  cent  of  instances  and  per- 
haps in  all:  it  is  usually  combined  both  in  the  lungs  and  in 
the  bronchi  with  one  of  the  pyogenic  cocci. 

The  severity  of  the  injury  to  the  walls  of  bronchi  result- 
ing in  continued  infection  with  a  variety  of  bacteria, 
appears  to  be  the  factor  determining  failure  of  resolution 
and  the  persistence  of  bronchopneumonia. 

The  Relation  of  Unresolved  Bronchopneumonia  to  Inter- 
stitial Suppurative  Pneumonia  Caused  by  Hemolytic  Strep- 
tococci.— Hemolytic  streptococci  have  been  present  in  a 
considerable  proportion  of  those  who  have  had  unresolved 
bronchopneumonia  and  its  occurrence  in  the  bronchi,  lung 
and  blood  of  the  heart  indicates  that  it  has  had  an  impor- 
tant part  in  causing  death.  Unresolved  bronchopneumo- 
nia, following  measles,  designated  by  MacCallum  "inter- 
stitial bronchopneumonia"  in  a  series  of  autopsies  at  Fort 
Sam  Houston  in  the  spring  of  1918,  was  constantly  asso- 
ciated with  hemolytic  streptococci.  Among  the  lesions  de- 
scribed as  interstitial  bronchopneumonia  was  at  least  one 
which  was  evidently  what  we  have  designated  interstitial 
suppurative  pneumonia.  Lymphangitis  was  not  infre- 
quently found  with  "interstitial  bronchopneumonia"  fol- 
lowing measles.  At  Camp  Lee  and  Camp  Dix,  following 
the  epidemic  of  influenza,  MacCallum  found  "interstitial 
bronchopneumonia"  with  no  hemolytic  streptococci  and 
noted  that  lymphatics  in  the  interstitial  septa  were  incon- 
spicuous and  that  none  was  found  distended  with  exudate; 
empyema  was  not  present. 

We  have  shown  that  interstitial  suppurative  pneumonia 
is  an  acute  lesion  caused  by  hemolytic  streptococci.  Unre- 
solved bronchopneumonia  is  accompanied  by  chronic  pneu- 
monia and  has  no  necessary  relation  to  this  microorganism. 


PATHOLOGY  AND  BACTEIUOLOO  Y  FOLLOWING  INFLUENZA     279 

In  a  foregoing  section  we  have  described  instances  of  in- 
terstitial suppurative  pneumonia  unaccompanied  by  chronic 
changes,  and  in  the  present  section  we  have  described  in- 
stances of  unresolved  bronchopneumonia  with  no  infection 
by  hemolytic  streptococci.  We  have  pointed  out  that  the 
incidence  of  streptococcus  infection  with  unresolved  bron- 
chopneumonia does  not  materially  differ  from  that  willi 
acute  bronchopneumonia  even  though  the  greater  duration 
of  the  disease  gives  more  opportunity  for  infection.  In 
some  of  the  autopsies  made  by  MacCallum  at  Fort  Sam 
Houston,  lesions  of  streptococcus  infection  doubtless  coex- 
isted with  unresolved  bronchopneumonia. 

In  the  3  autopsies  described  below,  interstitial  suppura- 
tive pneumonia  with  empyema  caused  by  hemolytic  strepto- 
coccus occurs  in  association  with  unresolved  broncho- 
pneumonia. 

Autopsy  420. — J.  E.  S.,  white,  aged  thirty-two  years,  born  in  England 
and  resident  of  Los  Angeles,  Cal.,  had  been  in  military  service  one  month. 
Onset  of  illness  began  on  October  3,  eleven  days  before  his  death.  He  was 
admitted  to  the  hospital  on  the  following  day  with  the  diagnosis  of  influenza 
and  acute  bronchitis.  Pneumonia  believed  to  be  lobar  was  recognized  eight 
days  after  admission. 

Anatomic  Diagnosis. — Unresolved  bronchopneumonia  with  hemorrhagic 
peribronchiolar  consolidation  in  right  lung;  interstitial  suppurative  pneumonia 
with  consolidation  in  left  upper  lobe;  fibrinopurulent  pleurisy;  purulent  bron- 
chitis. 

The  left  pleural  cavity  contains  200  e.e.  of  turbid  yellow  fluid  in  which 
are  flakes  of  fibrin.  In  the  inner  and  upper  part  of  the  left  upper  lobe  there 
is  an  area  of  consolidation  where  the  tissue  has  a  cloudy,  pinkish  gray  color 
and  is  finely  granular  on  section.  Here  the  interstitial  septa  are  distended  by 
edema,  so  that  they  are  in  places  0.5  c.e.  across;  in  some  spots  they  have  a 
bright  yellow  color.  In  the  posterior  parts  of  the  middle  and  lower  lobes 
there  is  flabby  consolidation  where  the  tissue  has  a  cloudy,  red  color  with 
scattered  ill-defined  yellow   spots. 

Bacteriologic  examination  shows  the  presence  of  hemolytic  streptococci 
in  the  blood  of  the  heart;  hemolytic  streptococci  with  B.  influenza?  and  S. 
aureus  in  the  left  lung  and  S.  hemolyticus  with  S.  aureus  in  the  right  lung. 

Microscopic  examination  shows  that  bronchi,  bronchioles,  alveolar  ducts 
and  the  greater  part  of  the  infundibula  are  filled  with  polynuelear  leucocytes, 
whereas  the  alveoli  surrounding  these  structures  contain  fibrin.  The  walls 
of  the  small  bronchi  are  thickened  and  contain  mononuclear  cells;  the  adjacent 


280      PNEUMONIAS  AND   INFECTIONS  OF   RESPIRATORS   TRACT 

alveolar  walls  are  similarly  infiltrated  and  thickened  and  the  fibrin  within 
them  is  undergoing  organization,  being  invaded  by  plasma  cells,  fibroblasts 
and  ne.wly  formed  blood  vessels.  In  some  sections  interstitial  septa  are  dis- 
tended l'\  edema  and  contain  fibrin  in  abundance;  in  places  the  tissue  contains 
polynuclear  leucocytes  closely  packed  together.  There  are  lymphatics  greatly 
distended  by  polynuclear  leucocytes  with  some  fibrin,  lymphocytes  and  red 
bl 1  corpuscles. 

Autopsy  428. —  I).  11. .  while,  aged  twenty-five,  a  farmer  from  Oklahoma, 
had  been  in  military  service  three  weeks.  Onset  of  illness  was  on  September 
21,  twenty-five  'lavs  before  death,  with  fever,  cough  and  mucopurulent  ex- 
pectoration. The  patient  w.is  admitted  with  the  diagnosis  of  acute  bilateral 
bronchitis.  Pour  days  Inter  bronchopneumonia  was  recognized,  and  subse- 
quently there  was  otitis  media  and  empyema;  600  c.c.  of  thin,  purulent  fluid 
were  aspirated  from  the  right  chest  three  days  before  death. 

Anatomic  Diagnosis. — Unresolved  bronchopneumonia;  suppuration  of  in- 
terstitial tissue  of  upper  right  ami  lower  left  lobes;  purulent  bronchitis; 
fibrin opurulent  pleurisy;  thoracotomy  wound  at  the  base  of  the  righl  chest; 
collapse  of  both   lungs;   serofibrinous  pericarditis. 

The  left  pleural  cavity  contains  ;">()  c.c.  of  turbid  seropurulenl  fluid  in 
which  are  numerous  Hakes  of  soft  fibrin.  The  right  pleural  cavity  contains 
150  c.c.  of  similar  fluid.  The  mediastinum  is  edematous.  The  pericardial 
cavity  contains  50  c.c.   of  yellow  fluid. 

The  right  lung  is  moderately  collapsed.  In  the  upper  and  lower  lobes  are 
small  patches  of  red,  lobular  consolidation.  The  upper  third  of  the  upper 
lobe  is  laxly  consolidated  and  near  its  inner  surface  the  interstitial  septa  are 
thickened  to  from  1  to  1.5  mm.  in  width,  and  at  intervals  occur  bead-like 
swellings  from  which  creamy  purulent  fluid  exudes  upon  the  cut  surface.  In 
the  left  lung  small  patches  of  gray  consolidation  occur  throughout  the  lower 
lobe  and  here  the  interstitial  septa  are  thickened,  beaded  and  contain  puru- 
lent  fluid. 

Bacteriologic  examination  shows  that  the  Mood  contains  S.  henmlyt  icus : 
from  the  right  lung  and  from  the  right  main  bronchus  hemolytic  streptococci 
and  B.  influenza?  are  grown. 

Microscopic  examination  shows  that  the  epithelium  of  the  bronchi  lias 
undergone  hypertrophy;  the  wall  is  infiltrated  with  lymphoid  ami  plasma 
cells  and  thickened  by  new  formation  of  fibrous  tissue;  there  is  similar  thicken- 
ing of  adjacent  alveolar  septa  and  alveoli,  often  lined  by  cubical  cells,  are 
diminished  in  size.  Connective  tissue  about  the  blood  vessels  and  the  inter- 
stitial septa  are  thickened  and  infiltrated  with  mononuclear  cells.  In  parts 
id'  the  lung  the  interstitial  septa  are  edematous  and  contain  polynuclear  leu- 
cocytes, in  some  places  in  great  number.  Lymphatics  are  greatly  dilated  and 
filled  with  polynuclear  leucocytes  which  in  the  center  of  some  lymphatics  have 
undergone  necrosis.  In  one  place  a  small  abscess  is  in  contact  with  a  de- 
fended lymphatic  Lymphatics  contain  ( i  ra  m-sta i ning  cocci  in  pairs  and  short 
ehains,  present  in  immense  number  where  uecrosis  has  occurred. 

Autopsy  -433. — B.  .L,  white,  aged  twenty-seven,  from  Arkansas,  has  been 
in  military  service   one   mouth.     Onset  of  illness  was   on   September  28,  nine- 


PATHOLOGY  ANM)   BACTERIOLOGY   FOLLOWING    I  N  FL1  'KX/A     281 

teen  days  before  death,  with  cough  and  expectoration.     Pneumonic  consolida 
tion  was  recognized  two  days  later  and  20  c.c.  of  cloudy  fluid  were  aspirated 
from  the  left  chest  on   the   same   day.     Hemolytic   streptococci    were    found 
in  a  culture  from   the  throat   nine   days  before   death. 

Anatomic  Diagnosis. — Unresolved  bronchopneumonia  with  peribronchiolar 
and  confluent  lobular  consolidation ;  interstitial  suppuration  of  the  righl  lower 
lobe;   purulent  bronchitis;  fibrinopurulcnt  pleurisy. 

The  right  pleural  cavity  contains  7(io  c.c.  of  .yellowish  gray  purulent  fluid 
containing  flakes  of  fibrin.  The  left  pleural  cavity  contains  seropurulenl 
fluid  localized  over  the  external  part  of  the  lung. 

The  right  lung  is  voluminous  and  free  from  consolidation  save  at  the  lower 
and  posterior  part  of  the  lower  lobe  where  the  tissue  is  deep  red  and  studded 
with  firmer  spots  of  yellow  color  clustered  about  the  bronchi.  In  places 
the  interstitial  septa  are  thickened  and  yellow.  Surrounding  some  of  the 
bronchi    near    the    apex    of    the    left    lung    are    red    patches    of    consolidation. 

Culture  from  heart's  blood  remained  sterile.  S.  hemolyticus  was  grown 
from  right  pleural  cavity,  and  S.  hemolyticus  and  B.  influenzae  were  grown 
from  the  right  lung.  Culture  from  the  left  lung  contained  S.  aureus  and 
contaminating  microorganisms. 

Microscopic  examination  shows  the  presence  of  peribronchiolar  patches  of 
pneumonia  in  which  there  are  few  polynuclear  leucocytes  and  many  lymphoid 
and  plasma  cells;  the  alveolar  walls  are  thickened  and  infiltrated  with  mono- 
nuclear cells.  In  some  sections  the  tissue  is  wholly  consolidated  and  the  site 
of  advanced  organizing  pneumonia.  Interlobular  septa  and  connective  tissue 
about  blood  vessels  are  thickened  and  cellular.  Small  bronchi  have  lost  their 
epithelial  lining,  their  walls  are  thickened  and  there  is  peribronchial  organ- 
izing pneumonia.  In  some  sections  the  lymphatics  are  immensely  dilated  and 
distended  with  polynuclear  leucocytes.  There  is  necrosis  of  the  walls  of  the 
lymphatics  and  of  the  polynuclear  leucocytes  within  the  lumen. 

In  the  discussion  of  acute  bronchopneumonia  it  has  been 
shown  that  S.  hemolyticus  is  not  infrequently  a  secondary 
invader  of  a  pneumonic  lesion  perhaps  caused  by  pneumo- 
cocci.  With  progress  of  the  disease  hemolytic  strepto- 
cocci persist.  In  the  autopsies  with  unresolved  pneumo- 
nia just  described,  hemolytic  streptococci  have  found  their 
way  into  the  lymphatics  and  produced  suppurative  lym- 
phangitis with  inflammation  of  the  interstitial  septa  of  the 
lung. 


CHAPTEE  V 

SECONDARY   [NFECTION   IX  THE  WARD 
TREATMENT  OF  MEASLES 

James  C.  Small,  M.D. 

A  study  of  !)"!'  cases  of  measles  Mas  made  in  the  base 
hospitals  of  Camps  Funstoii  and  Pike  from  July  to  Decem- 
ber, 1918,  with  the  purpose  of  establishing  any  existing  re- 
lation between  the  prevalence  of  the  hemolytic  streptococci 
and  the  incidence  of  the  graver  complications  of  measles, 
especially  the  pneumonia  following  measles.  The  greater 
number  of  these  cases  occurred  at  Camp  Pike  coineidently 
with  the  influenza  epidemic,  so  that  the  picture  is  modified 
during  this  period  by  a  summation  of  the  after  effects  of 
the  two  diseases. 

The  work  undertaken  includes: 

(a)  Pontine  throat  cultures  on  admission  of  all  patients 
with  measles. 

(b)  Separation  and  treatment  in  separate  wards  of  the 
patients  harboring  hemolytic  streptococci  and  those  free 
from  such  streptococci. 

(c)  Investigation  of  the  bacteriology  of  all  cases  under 
treatment,  by  weekly  throat  cultures  during  the  period  in 
the  hospital. 

(d)  Bacteriologie  study  of  the  complications  of  measles 
during  life  and  at  autopsy. 

(e)  Study  of  the  throat  bacteriology  of  men  on  duty  in 
the  camp,  to  establish  the  prevalence  of  hemolytic  strep- 
tococci and  of  B.  influenzae  in  normal  individuals. 

The  work  is  further  divided  into  that  done  at  Camp 
FWstoi]  during  the  latter  pail  of  July  and  throughout 
August,  and  that  done  at  Camp  Pike  during  September. 
October,  November  and  December,  1918. 


SECONDARY  INFECTION  IN  WARD  TREATMENT  OF   MEASLES    283 

Studies  at  Camp  Funston. — The  work  done  at  Camp 
Funston  is  limited  strictly  to  the  identification  of  hemo- 
lytic streptococci  in  the  throats  of  all  patients  with  measlos 
coming  into  the  base  hospital  at  Ft.  Riley  and  to  the  same 
study  of  a  group  of  normal  men  on  duty.  During  the 
period  of  study  hemolytic  streptococci  were  identified  by 
throat  culture  in  about  1  in  5  of  all  the  normal  men  ex- 
amined. Two  instances  of  otitis  media  represent  the  only 
complications  developing  in  the  112  cases  of  measles.  Cul- 
tures from  both  patients  showed  staphylococci.  The  entire 
absence  of  streptococcus  complications  appears  the  more 
surprising  in  view  of  the  fact  that  the  prevalence  of  hemo- 
lytic streptococci  among  patients  under  treatment  in  the 
ward  was  for  a  time  as  great  as  that  among  the  normal 
men.  No  special  hospital  management  wTas  instituted  on 
the  basis  of  the  findings  in  throat  culture.  S.  hemolyticus 
carriers  remained  in  the  wards  and  were  treated  alongside 
the  "clean"  cases.  The  sheet  cubicle  system  was  used  for 
bed  patients.  Face  masks  were  not  worn.  Convalescent 
patients  were  not  segregated,  and  they  assisted  in  the  care 
of  the  bed  patients  and  in  the  ward  kitchen.  After  the 
initial  throat  culture  on  admission,  the  throats  were 
gargled  with  argyrol  and  afterwards  sprayed  with  the  same 
solution  three  times  a  day.  This  solution  was  also  em- 
ployed to  relieve  the  discomfort  caused  by  the  conjunctivitis 
during  the  acute  stage  of  the  disease. 

Throat  Culture  and  Identification  of  Hemolytic  Strep- 
tococci.— In  general  the  methods  for  the  isolation  and 
identification  of  hemolytic  streptococci  as  adopted  by  the 
Medical  Department  of  the  Army  were  used.  All  organ- 
isms were  isolated  in  pure  culture,  grown  in  broth,  exam- 
ined microscopically  and  subjected  to  tests  for  hemolysis, 
(a  5  per  cent  suspension  of  sheep  corpuscles  being  em- 
ployed) ,  and  for  bile  solubility. 

Beef  infusion  broth  and  beef  infusion  agar  constituted 
the  two  basic  media  used.     They  were  prepared  so  that  the 


284      PNEUMONIAS  ami    INFECTIONS  OF   RESPIRATOR!    TRACT 

finished  producl  titrated  aboul  0.3  per  cent  acid  to  phe- 
oolphl  kalein. 

Brotli  tubes  were  carried  to  the  bedside,  hi  swabbing, 
the  attempt  was  made  to  produce  gagging.  This  causes 
the  tonsils  to  protrude  Prom  behind  the  anterior  pharyn- 
geal pillars  and  places  a  slighl  tension  en  the  capsule  which 
lends  to  squeeze  material  from  the  crypts.  The  surfaces 
of  (he  tonsils  thus  protruding  toward  the  midline  were 
brushed  quickly  with  a  small  cotton  swab  which  was  Lastly 
touched  to  the  posterior  pharyngeal  wall  and  withdrawn  so 
as  to  avoid  touching  any  other  parts.  The  swab  was  im- 
mediately ini reduced  into  a  tube  of  broth,  twirled  freely 
under  the  surface  of  the  liquid  and  discarded.  The  ma- 
terial thus  washed  into  the  broth  was  carried  to  the  labo- 
ratory and  kept  in  the  ice  bos  until  plating,  which  was  ac- 
complished with  as  little  delay  as  possible. 

Tubes  of  melted  agar  containing  12  c.c.  cooled  below 
45°  C,  after  receiving  0.6*  c.c.  of  sterile  deflbrinated  horse 
Mood,  were  inoculated  with  a  loopful  of  this  broth.  Thor- 
ough mixing  and  pouring  into  Petri  dishes  (10  cm.  diam- 
eter) followed.  After  cooling,  a  second  loopful  was 
st  leaked  over  the  surface  of  one  half  of  the  plate.  Deep 
and  superficial  planting  were  thus  effected  on  the  same 
plate. 

This  method  was  found  to  he  very  useful.  It  can  he  used 
with  advantage  provided  one  is  not  called  upon  to  make 
a  great  number  of  cultures  when  its  time  consuming  factor 
is  a  greal  inconvenience.  Another  disadvantage  is  the  dif- 
ficulty of  picking  single  colonies  for  subculture.  Tn  spite 
of  the  most  careful  selection  and  fishing  of  a  dee])  colony, 
subcultures  are  less  likely  to  he  pure  than  when  surface 
colonies  are  chosen.  By  careful  regulation  of  the  amount 
of  agar  in  the  tubes,  the  addition  of  a  measured  amount 
of  blood  to  each  enabled  one  to  pour  standard  blood  agar 
plates.  Uniform  thorough  mixing  of  the  blood  is  essential 
so  that  the  plate  may  present  the  desired  "silky"  rather 


SECONDARY  INFECTION   IN    WARD  TREATMENT  OE   MEASLES    285 

than  a  " curdled"  appearance  when  viewed  by  transmitted 
light. 

The  plates  wore  incubated  eighteen  to  twenty-four  hours 
when  subcultures  in  broth  were  made  from  the  hemolytic 
colonies.  After  growing  those  for  a  similar  period  the 
additional  tests  were  carried  out  as  indicated  above. 

Hemolytic  Streptococci  with  Measles. — The  incidence  of 
hemolytic  streptococci  in  the  throats  of  patients  with 
measles  admitted  to  the  base  hospital  at  Ft.  Riley  was 
found  to  be  remarkably  small. 


Table  LV 

Hemolytic   Streptococci   with   Measles   in  all  Patients  Adm 
Wards  at  Camp  Funston 

ITTED  TO  THE 

days  in 
hospital 

approx- 
imate DAY 
OF    DISEASE 

NO.     OF 
PATIENTS 
CULTURED 

NO.  WITH 
HEMOLYTIC 
STREPTO- 
COCCI 

PER  CENT 
WITH    HEMO- 
LYTIC 
STREPTO- 
COCCI 

First  Culture 
Second  Culture 
Third  Culture 

0  to     1 
3  to  10 
8  to  23 

1  to     8 

4  to  16 

12  to  26 

112 

86 
58 

3 
11 
14 

2.67 
12.79 
24.14 

The  first  culture  represents  the  findings  on  admission,  in  a  series  of  112 
cases;   86  patients  being  cultured  twice;   58  patients  three  times. 

Of  the  112  cases  examined  on  admission  only  3,  or  2.67 
per  cent  were  found  to  carry  hemolytic  streptococci.  Those 
patients  who  were  recultured  after  from  three  to  ten  days 
in  the  hospital  showed  an  incidence  of  12.8  per  cent.  A 
third  culture  including  patients  from  eight  to  twenty-three 
days  in  the  hospital,  showed  an  incidence  of  24.1  per  cent. 

Hemolytic  Streptococci  in  the  Throats  of  Normal  Men. — 
A  total  of  274  throat  cultures  from  normal  men  on  duty  at 
Camp  Funston  (Table  LVI)  shows  that  21.9  per  cent  car- 
ried hemolytic  streptococci  at  a  time  when  there  were  few 
upper  respiratory  infections  in  the  camp.  A  small  group 
of  men  resident  in  the  hospital  shows  a  slightly  higher 
prevalence  of  hemolytic  streptococci  (29.3  per  cent). 

The  figures  in  Table  LVI  are  in  sharp  contrast  with 
those  for  measles  patients  on  admission  to  the  hospital. 


286      PNEUMONIAS  AND   INFECTIONS  OF  RESPIRATORY   TRAIT 


Table  LYI 
Incidence  op  Hemolytic  Streptococci,  Camp  Funston. 


f£   5 

7.    ~. 

P    < 

w 

HEMOLYTIC 

STREPTOCOCCI 

PRESENT 

PER  CENT  WITH 

HEMOLYTIC 

STREPTOCOCCI 

(id    White  Men: 

70th    Int'antrv 

24 

4 

16.7 

210th  Engineers,  Co.  C 

26 

6 

23.1 

164th   Depol    Brigade,  Co.  15 

50 

Pi 

20.0 

L64th  Depol  Brigade,  Co.  18 

51 

13 

25.5 

164th  Depot  Brigade,  Co.  28 

50 

13 

26.0 

Total 

201 

46 

22.9 

{b)    Colored   Men, 

Detent  ion  <  'amp  No.  2  : 

T  * "  4 1  i i   Depot   Brigade,  Prov.  Co.  22 

25 

6 

24.0 

3d   Development   Battalion,  Co.  A 

24 

3 

12.5 

.'M    Development  Battalion,  Co.  D 

24 

5 

20.8 

Total 

73 

14 

19.2 

(c)   Men  resident  in  the  hospital: 

Laboratory  workers 

10 

Q 

30.0 

Patients  in  surgical  ward 

14 

4 

28.6 

24 

7 

29.3 

T\yo  organizations  from  which  normal  men  were  chosen 
for  examination  Furnished  a  considerable  number  of  cases 
of  measles  and  offer  data  (Table  LVII,  A  and  B)  for  fur- 
ther comparison. 

Table  LVII 

A.  Hemolytic  Streptococci  with   Measles  in  164th  Depot  Brigade, 

Company  28. 


days  in 
hospital 

NO.    OF 

NUMBER   WITH 

PER  CENT  WITH 

patients 

HEMOLYTIC 

HEMOLYTIC 

CULTURED 

STREPTOCOCCI 

STREPTOCOCCI 

First  Culture 

0  to    1 

23 

0 

0 

Second  Culture 

3  to     9 

23 

4* 

17.4 

Third  Culture 

10  to  21 

21 

4 

19.05 

Normal  men  of 

Co.  28 

50 

13 

26.00 

B.  Hemolytic  Streptococci  with   Measles  in  Seventieth  Infantry 


First  Culture 

0  to     1 

38 

0 

0 

Second  Culture 

.1  to     9 

25 

1 

4.0 

Third  Culture 

8  to  17 

12 

2 

16.7 

Normal  men  on  duty 

with  70th   Infantry 

24 

4 

16.7 

'Two  cases   positive   for  hemolytic   streptococci  on   this   examination  were  negative  on 
next  examination. 


SECONDARY  INFECTION  IN  WARD  TREATMENT  OF  MEASLES    287 

No  one  of  the  61  cases  of  measles  from  the  two  organ- 
izations was  found  to  be  positive  on  admission  to  the  hos- 
pital. Yet  among  normal  men  in  one  of  these  organiza- 
tions the  incidence  of  hemolytic  streptococci  was  26  per  cenl 
and  in  the  other,  16.7  per  cent.  In  both  organizations  the 
incidence  among  normal  individuals  compares  closely  with 
that  of  the  patients  after  a  period  in  the  measles  wards 
of  the  hospital. 

Discussion. — Three  features  of  the  data  collected  at 
Camp  Funston  are  noteworthy.  First,  the  small  percent- 
age of  S.  hemolyticus  carriers  among  the  men  admitted  to 
the  hospital  with  measles  as  compared  with  the  percentage 
found  in  normal  men  in  the  camp.  Second,  the  increase 
in  the  number  of  S.  hemolyticus  carriers  among  patients 
during  their  stay  in  the  hospital,  the  increase  continuing 
until  it  approaches  that  of  the  normal  men  on  the  outside. 
Third,  the  prevalence  of  hemolytic  streptococci  in  normal 
throats. 

In  comparing  men  arriving  at  the  hospital  acutely  ill 
with  measles  with  normal  men  in  the  organization  from 
which  they  came,  only  one  variable  can  be  found  on  which 
to  base  the  differences  observed  in  the  two  groups.  This 
is  the  advent  of  the  acute  disease.  The  figures  seem  to  sug- 
gest a  temporary  disappearance  of  hemolytic  streptococci 
from  the.  throats  of  patients  acutely  ill  with  measles,  at 
least,  to  such  an  extent  that  the  same  cultural  methods  fail 
to  identify  the  organisms. 

The  increase  in  the  S.  hemolyticus  carriers  among  pa- 
tients with  measles  after  a  period  in  the  hospital  might 
depend  upon  two  factors:  First,  the  exposure  to  contact 
infections  in  the  hospital  ward,  depending  on  the  length 
of  time  in  the  ward  as  well  as  on  the  character  of  the  ward 
management;  second,  the  passing  of  the  acute  stage  of 
measles  with  a  return  of  the  bacterial  flora  of  the  throat  to 
the  condition  existing  before  the  onset  of  the  acute  disease. 
The  first  appears  the  more  probable.     The  second  has  only 


1>S      PNEUMONIAS  AND   [NFECTIONS  OF  RESPIRATOR1    TRA< 


'T 


Hie  supporl  of  the  observation  thai  the  streptococci  were 
absenl  from  tlie  throat  during  the  acute  stage  of  measles 
or  were  much  less  frequently  Pound  in  patients  with  measles 
than  in  normal  men  and  later  their  incidence  approached 
that  in  norma]  individuals.  The  rather  high  incidence  of 
hemolytic  streptococci  in  normal  men  at  ('amp  Funston  may 
have  been  due  to  the  very  recent  assembling  of  the  10th 
Division  which  now  occupied  the  cam]).  It  is  probable  that 
the  housing  of  large  numbers  of  men  in  barracks  is  at- 
tended by  the  same  contact  dissemination  of  mouth  organ- 
isms that  occurs  in  hospital  wards. 

Measles  at  Camp  Pike. — All  cases  of  measles  coming  into 
the  base  hospital  at  Camp  Pike  between  September  15  and 
December  15,  1918,  a  total  of  867  cases,  are  included  in  the 
report.  Upon  the  arrival  of  the  commission  at  Camp  Pike 
early  in  September,  a  plan  for  the  separation  of  cases  car- 
rying hemolytic  streptococci  and  those  free  from  these  or- 
ganisms was  put  into  operation.  The  preliminary  arrange- 
ments included  the  allotment  of  suitable  wards  for  treat- 
ment of  the  different  classes  of  cases;  a  throat  culture  sur- 
vey of  all  patients  with  measles  under  treatment  at  the 
time;  their  separation  in  accordance  with  the  results  of 
bacteriologic  examination,  and  the  transfer  of  each  group 
of  patients  to  its  designated  ward.  By  September  15  these 
preliminary  arrangements  had  been  completed.  Cases  of 
measles  admitted  on  this  date  and  afterwards  were  held  in 
an  observation  ward  pending  the  report  upon  a  throat  cul- 
ture before  they  were  transferred  to  the  treatment  wards. 

Beginning  September  15  the  following  system  of  hand- 
ling measles  cases  was  maintained  in  the  wards  of  the  base 
hospital. 

All  patients  were  received  in  an  observation  ward  where 
they  remained  until  the  results  of  a  throat  culture  for  hemo- 
lytic streptococci  could  be  reported  back'  to  the  wai'd. 
( lases  reported  positive  or  negative  were  immediately  trans- 
ferred to  their  respective  treatment  wards.     .Ml  patients  in 


SECONDARY  INFECTION    IN   WAED  TKEATMENT  OF   MEASLES    289 

the  treatment  wards  were  cultured  al  intervals  of  one  week 
and  cases  found  positive  were  1  ransferred  from  1  lie  "clean" 
treatment  wards  to  a  treatment  ward  for  cases  carrying 
hemolytic  streptococci.  The  ward  personnel  attending  pa- 
tients in  the  "clean"  treatment  wards  was  examined  by 
throat  cultures  from  time  to  time  with  the  purpose  of  elim- 
inating- S.  hemolyticus  carriers.  Patients  segregated  in  the 
streptococcus  wards  remained  there,  if  uncomplicated, 
throughout  their  hospital  treatment  even  though  subse- 
quent repeated  throat  cultures  showed  that  the  carrier  con- 
dition had  disappeared.  Two  wards  were  provided  to  care 
for  the  pneumonia  following  measles.  One  received  only 
patients  whose  throat  cultures  were  negative  for  hemolytic 
streptococci;  the  other,  those  positive.  It  is  essential  that 
the  throat  culture  on  which  this  differentiation  is  made  he 
taken  as  soon  as  the  complication  is  reported  and  that 
transfer  be  made  promptly  on  receipt  of  the  report  of  the 
culture.  To  facilitate  this  transfer,  cases  of  pneumonia 
complicating  measles  were  reported  to  the  laboratory  as 
soon  as  diagnosed  and  cultures  were  taken  at  once.  The 
case  remained  in  the  measles  Avard  during  twenty-four 
hours,  isolated  as  well  as  possible,  awaiting  report  of  cul- 
ture before  transfer.  Within  the  positive  ward  for  measles 
pneumonias,  distinction  was  made  between  streptococcus 
pneumonias  and  nonstreptoeoceus  pneumonias  harboring 
hemolytic  streptococci  in  their  throats.  The  two  classes  of 
cases  were  treated  in  separate  sections  of  the  ward. 

Ear  complications  were  seen  and  treated  by  medical  of- 
ficers from  the  otological  service.  These  patients  remained 
in  the  measles  wards  while  in  the  acute  stage  of  measles, 
but  later  wrere  transferred  to  the  service  of  otology  when- 
ever further  surgical  treatment  became  necessary. 

Within  the  individual  wards  for  treatment  of  measles 
and  measles  pneumefnias,  precautions  for  minimizing  the 
dangers  of  contact  infections  were  carried  out  as  well  as 
possible.     Throughout  the  study  we  had  the  hearty  cooper- 


290      PNEUMONIAS  ami   [NFECTIONS  OF   RESPIRATOR'S  TRACT 

ation  of  the  base  hospital  authorities  and  earnest,  well- 
directed  effOrl  to  perfecl  ward  management  on  the  part  of 
the  ward  surgeons  and  their  staffs.     Difficulties  encoun- 
tered during  the  emergency  created  by  the  sudden  explosion 
of  ilif  influenza  epidemic,  in  spile  of  the  besl  efforts  of  all, 
did  much  to  disrupt  the  plan  which  had  been  instituted  for 
the  control  and  study   of    the    complications    of   measles. 
Scarcely  had  wards  been  designated  and  all  measles  pa- 
tients on  hand  differentially  allotted  to  them,  when  the  in- 
fluenza  epidemic  appeared  and   quickly   Tilled   the  hospital 
beyond  its  capacity.     Measles  wards  were  taken  over  For 
the  care  of  influenza  patients.     Measles  patients,  of  which 
there  were  not  a  great  number  at  the  time,  were  necessarily 
crowded  together,  so  that  compartments  of  wards  instead 
of  separate  wards  had  to  be  used  in  maintaining  our  sep- 
aration of  the  two  groups  of  patients.     While  the  base  hos- 
pital was  yet  filled  with  patients  with  influenza  and  in- 
fluenza pneumonia,  admission  of  patients  with  measles  in- 
creased, so  that  one  ward  after  another  was  reclaimed  for 
the  care  of  this  disease.     During  this  period  the  measles 
wards  were  at  times  overcrowded  and  the  strictest  ward 
technic  could  not  he  practiced.     Again  new  wards  were, 
on  occasions,  partly  filled  by  admission  and  transfer  before 
they  were  properly  equipped  to  receive  patients.     This  dis- 
organization was  directly  due  to  the  necessity  of  treating 
a  rapidly  increasing  number  of  measles  patients  before  the 
hospital  was  cleared  of  patients  with  influenza  and  pneumo- 
nia. After  this  emergency,  the  system  of  ward  management 
was  rapidly  readjusted,  and  admissions  were  limited  to  the 
normal  capacities  of  the  wards. 

The  cubicle  system  was  used  in  all  wards.  Bed  patients 
were  not  required  to  wear  masks,  but  the  mask  was  strictly 
enforced  upon  all  patients  leaving  the  cubicle.  All  attend- 
ants were  required  to  wear  gowns,  caps  and  masks  while 
in  the  wards.  An  attempt  was  made  to  prevent  the  congre- 
gating of  convalescents.     Guards  were  posted  at  the  latrine 


SECONDARY  INFECTION  IN  WARD  TREATMENT  03?   MEASLES    201 

doors  to  limit  admission  to  the  capacity  of  the  latrine.  Bor- 
rowing and  lending  of  any  materials  between  patients  were 
strictly  forbidden.  Paper  sputum  cups  were  provided, 
kept  clean  and  covered.  In  the  measles  pneumonia  wards 
hand  disinfectant  solutions  were  provided  for  use  by  at- 
tendants when  they  passed  from  one  patient  to  another. 
The  ward  floors  were  scrubbed  at  intervals  with  lysol  in 
water.  Dry  sweeping  of  the  wards  in  the  morning  is  re- 
grettable. 

Bacteriologic  Methods  Used  in  the  Study. — The  methods 
used  for  the  identification  of  hemolytic  streptococci  here 
were  essentially  the  same  as  those  used  at  Camp  Funston 
and  described  above,  the  one  exception  being  the  use  of 
surface  cultures  on  blood  agar  instead  of  the  combined  sur- 
face and  deep  culture.  Blood  agar  plates  containing  5  per 
cent  defibrinated  horse  blood  were  poured  and  used  while 
fresh.  The  throat  swabs  were  carried  to  the  laboratory  in 
sterile  test  tubes.  The  plates  were  inoculated  by  touching 
the  swab  lightly  to  the  surface  of  the  agar  plate  at  two 
places,  one  near  either  extremity  of  a  given  diameter  of 
the  plate.  On  touching  the  swab  to  the  agar,  the  swab 
stick  was  rolled  between  the  fingers  so  as  to  turn  it  through 
one  revolution  and  thereby  bring  all  points  of  the  circum- 
ference of  the  cotton  swab  in  contact  with  the  agar  surface. 

The  material  thus  inoculated  on  the  plates  was  spread  by 
means  of  a  platinum  wire  slightly  turned  over  at  the  end  in 
"hockey  stick"  fashion.  The  wire  was  passed  back  and 
forth  several  times  over  the  point  of  inoculation  and  then 
multiple  streaks  and  cross  streaks  were  made  over  the  agar 
surface.  The  initial  contact  of  the  wire  with  the  point  of  in- 
oculation was  not  repeated.  The  cross  streaking  serves  to 
spread  and  distribute  this  material  evenly  over  the  surface. 
Well  seeded  plates  by  this  multiple  streak  method  are  the 
rule  and  the  uniform  distribution  of  well  separated  colonies, 
over  the  surface  makes  it  very  easy  to  pick  pure  cultures, 
and  renders  plate  reading  easy. 


292      PNEUMONIAS  AND   INFECTIONS  OF   RESPIRATORS  TBACT 

Very  early  in  the  course  of  our  study  of  throal  cultures 
a1  Camp  Pike,  the  greal  frequency  of  abundanl  growths  of 
\\.  influenzae  was  observed.  Consequently,  the  throat  cul- 
tures of  all  measles  patients  examined  Prom  September  15 
in  October  20  were  studied  for  the  identification  of  1>. 
influenzae.  In  all  cases  identification  was  based  on  the  cul 
tural,  staining  and  morphologic  characteristics.  Tests  for 
growth  on  hemoglobin  free  media  were  no1  made  as  a 
rout  inc. 

Relation  of  Measles  and  Pneumonia  Following  Measles 
to  the  Influenza  Epidemic. — The  influenza  epidemic  at 
Camp  Pike  was  recognized  on  September  23  because  of  an 
alarming  increase  of  hospital  admissions.  It  ran  its  brief 
course,  and  ten  days  later,  October  3,  the  decline  began. 
The  first  four  days  of  October  rank  highest  in  admissions 
of  patients  with  pneumonia  following  influenza.  The  onset 
of  20  scattered  cases  of  measles  occurred  before  Septem- 
ber 25,  and  later  the  number  slowly  increased  reaching  its 
height  about  the  middle  of  October;  after  this  time  a  grad- 
ual decline  began,  and  continued  during  about  three  weeks 
before  the  preepidemic  level  was  reached.  During  this 
period  of  six  weeks  following  September  25,  709  cases  of 
measles  occurred. 

Table  LYTII 

Onset   of   Measles   and   of   Pneumonia    Following   Measles   by   Weeks 
prow   September   11   to  December  11,  1918 


| 

PNEUMONIA 

Dates 

MEASLES 

FOLLOWING 

U  EASLES 

s  .pt. 

11 

to 

17 

18 

0 

Sept. 

IS 

to 

24 

20 

n 

Sept. 

25 

to 

Oct.   1 

74 

ii 

OH. 

o 

to 

8 

143 

i:; 

Oct. 

!) 

to 

15 

178 

9 

Oet. 

16 

to 

22 

158 

16 

Oct. 

L1:: 

to 

29 

Km 

n 

Oct. 

30 

to 

Nov.  5 

56 

3 

Nov. 

6 

to 

12 

.'',8 

1 

Nov. 

13 

to 

19 

2.1 

1 

Nov. 

20 

to 

2fi 

29 

1 

Nov. 

27 

to 

Dec.  3 

22 

1 

Dec. 

1 

to 

10 

8 

1 

Dec. 

11 

0 

1 

SECONDARY  INFECTION  IN  WARD  TREATMENT  OF   MEASLES    293 

Pneumonia  following  measles  began  to  appear  on  Octo 
ber  5,  and  within  the  week  following  L6  cases  occurred.  An 
equal  number  of  cases  appeared  each  week-  during  aboul 
three  weeks  and  fewer  scattered  eases  occurred  throughout 
November  and  December.  Table  LVi  1 1  shows  dale  of  onset 
of  measles  and  measles  pneumonia  cases. 

Chart  3  presents  the  occurrence  of  measles  and  of  the 
pneumonia  following  measles  by  weeks  of  onset  compared 
with  that  of  epidemic  influenza. 


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Chart  3. — Shows  the  relation  of  the  epidemic  of  measles  to  that  of  influenza  at  Camp 
Pike,  and  the  relations  of  the  pneumonia  following  measles  to  both  measles  and  influenza. 
The  large  incomplete  curve  represents  influenza;  the  intermediate  curve,  measles;  the 
small   curve,   pneumonia   following  measles. 


294      PNEUMONIAS  ANli   INFECTIONS  OF   RESPIRATORS   TRACT 


It  will  be  noted  from  the  overlapping  of  the  two  curves 
in  Charl  .'!  that  a  considerable  portion  of  the  measles  cases 
appeared  before  the  influenza  had  subsided  in  Camp  Pike. 
This  occurrence  of  the  two  epidemics  at  the  same  time 
makes  ii  impossible  to  separate  the  parts  played  by  cadi 
disease  in  producing  the  pneumonias  and  other  complica- 
tions following  measles.  Analysis  of  the  charl,  however, 
shows  that  the  pneumonia  with  measles  occurred  in  large 
part  during  the  first  hall'  of  the  measles  epidemic.  This 
is  of  particular  significance  since  it  was  during  this  period 
that  the  effects  of  the  influenza  wave  were  fell  most  se- 
verely. 

In  Table  LIX  the  cases  of  measles  are  grouped  into 
fifteen  day  periods  according  to  their  dates  of  onset  and 
the  pneumonias  arising  from  each  group  are  tabulated. 
This  tabulation  shows  very  clearly  that  the  pneumonia 
complications  developed  in  large  pari  in  patients  with 
measles  entering  the  hospital  during  the  influenza  period, 
that  is.  late  in  September  and  during  the  first  half  of 
October. 

Table  LIX 
Patients  with  Measles  and  with    Subsequent  Pneumonia 


HATES 

TOTAL    CASES    OF 

MEASLES    DURING 

INTERVALS      OF 

15  DAYS 

TOTAL     CASES    OF 
PNEUMONIA 
FROM     SAME 

PER    CENT 

INCIDENCE 

OK    PNEUMONIAS 

Sept. 

11  to  30 

861 

433 
347  ) 

14] 

16.28  1 

9.7% 

8.07   1 

U2 

Oct. 

1  to  15 

28  J 

0<-t. 

16  to  31 

270' 

8' 

2.96 

Nov. 

1    to  15 

91 

434 

2 

•14 

2.2 

3.295 

Nov. 

in  to  30 

56 

1 

7.15  J 

T)oc. 

1   to  15 

17 

o. 

The  high  incidence  of  pneumonia  among  measles  patients 
coming  into  the  hospital  prior  to,  with,  or  immediately  fol- 
lowing the  height  of  the  influenza  epidemic  is  very  striking. 
It  so  happens  that  half  of  the  total  number  of  measles  cases 


SECONDARY  INFECTION  JN   WARD  TREATMENT  OE   MEASLES    295 

considered,  date  their  onsets  prior  to  October  15.  Prom  the 
433  cases  included  in  this  first  half,  42  cases  of  pneumonia 
arose,  while  from  the  434  cases  arising  during  the  two 
months  following  October  15,  only  14  or  one-third  as  many 
cases  of  pneumonia  developed.  These  figures  very  strongly 
suggest  that  influenza  played  a  large  part  in  the  production 
of  the  pneumonia  with  measles  in  this  group  of  cases. 

Again  the  9.7  per  cent  incidence  of  pneumonia  in  the  first 
half  of  cases  considered,  approaches  the  12  per  cent  inci- 
dence of  pneumonia  following  influenza  observed  in  the  epi- 
demic at  Camp  Pike,  while  the  incidence  of  3.2  per  cent  in 
the  second  half  of  the  cases  conforms  more  nearly  to  figures 
for  pneumonia  following  measles  in  the  army  prior  to  the 
pandemic  of  influenza. 

It  has  been  shown  that  the  prevalence  of  B.  influenzae  at 
Camp  Pike  increased  with  the  passing  of  the  wave  of  in- 
fluenza (p.  40)  and  that  this  increase  applied  to  the 
measles  admissions.  For  a  time  the  separation  of  measles 
patients  carrying  B.  influenza?  as  identified  by  throat  cul- 
ture on  admission,  from  those  free  from  it,  was  practiced. 
All  cases  were  then  followed  up  by  weekly  throat  cultures, 
and  cases  in  negative  wards  on  being  identified  as  positives 
were  transferred. 

This  practice  was  discontinued  as  impractical  when  it 
became  apparent  that  about  80  per  cent  of  patients  with 
measles  would  be  found  positive  for  B.  influenza?  when  re- 
peated throat  cultures  were  made  during  their  hospital 
treatment.  The  dissemination  of  B.  influenza?  through  the 
wards  from  which  we  were  attempting  to  exclude  it  took 
place  much  faster  than  we  could  follow  its  spread  by  cul- 
tural methods.  When  this  became  evident,  the  practice 
of  separating  the  two  groups  of  patients  with  reference  to 
B.  influenza?  was  discontinued  and  the  great  inconvenience 
of  repeated  transfer  of  patients  was  largely  eliminated. 

Table  LX  gives  the  findings  in  426  cases  of  measles 
cultured  for  B.  influenza?  during  the  period  when  the  prac- 


296      PNEUMONIAS  AND   INFECTIONS  OF  RESPIRATOR'S  TRACT 


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SECONDARY  INFECTION   IN   WARD  TREATMENT  OF   MEASLES    297 

tice  of  separating  measles  patients  carrying  l'>.  influenzae 
from  those  not  carrying  the  organisms  was  followed. 

On  admission  35.6  per  cent  of  the  patients  were  found 
positive  for  B.  influenzae.  Repealed  throat  cultures  were 
not  confined  to  those  appearing  negative  on  this  initial  cul- 
ture, but  were  made  on  all  patients  without  regard  to  their 
being  previously  positive  or  negative.  By  a  summation 
of  the  results  of  the  weekly  cultures  of  all  patients,  the  per- 
centage of  patients  carrying  B.  influenzae  rises  from  35.6 
per  cent  on  admission,  to  62.7  per  cent  after  one  week; 
to  77.7  per  cent  after  two  weeks;  to  84  per  cent  after  three 
weeks  in  the  hospital. 

To  gain  some  idea  of  the  rate  of  spread  of  B.  influenzae 
in  wards  receiving  only  patients  whose  throat  cultures  were 
negative  for  B.  influenzae  on  admission,  a  similar  summa- 
tion of  the  results  of  repeated  throat  cultures  on  patients 
in  negative  wards  shows  weekly  increases  from  47.5  per 
cent  after  one  week,  to  68.1  per  cent  after  two  weeks;  to 
79  per  cent  at  the  end  of  three  weeks. 

These  results  demonstrate  quite  clearly  that  the  measles 
wards  were  saturated  with  B.  influenza?  during  the  period 
of  the  influenza  epidemic.  Conditions  within  the  measles 
wTards  with  regard  to  B.  influenzae  were  not  at  all  dif- 
ferent from  those  in  the  camp  community  during  this  pe- 
riod. "While  no  clinical  methods  could  be  relied  upon  to 
diagnose  influenza  in  the  presence  of  an  acute  attack  of 
measles,  there  is  every  reason  to  believe  that  the  occurrence 
of  clinical  influenza  with  measles  was  no  less  frequent  than 
was  its  incidence  in  the  camp  at  large,  that  is,  about  20  to 
25  per  cent.  That  influenza  played  a  large  part  in  deter- 
mining predisposition  to  the  complications  of  measles  in 
this  series  seems  evident. 

Hemolytic  Streptococci  with  Measles  at  Camp  Pike 

Between  September  15  and  December  15,  1918,  867  cases 
of  measles,  admitted  to  the  wards  of  the  base  hospital,  were 


L'l|S      PNEUMONIAS  A.ND   INFECTIONS  OF   RESPIRATORS   TRACT 

studied  and  handled  according  to  the  system  outlined 
above.  AJbOul  one  half  of  these  cases  appeared  during  tin' 
firsl  month  of  the  study.  During  this  month  hemolytic 
streptococci  played  a  very  Lnsignificanl  role.  This  micro- 
organism did  aol  appear  with  alarming  prevalence  until 
after  the  wards  had  been  thoroughly  overcrowded.  After 
the  emergency,  when  better  ward  conditions  were  provided, 
S.  hemolyticus  carriers  continued  to  develop  in  the  wards 
and  were  removed  when  identified.  The  first  S.  hemolyti- 
cus carriers  to  develop  in  the  wards  were  identified  on  Oc- 
tober  8.  The  first  case  of  streptococcus  pneumonia  de- 
veloped on  October  17,  while  streptococcus  otitis  as  a  com- 
plication of  measles  did  not  begin  until  a  little  later.  Driv- 
ing the  latter  two  mouths  of  the  study,  S.  hemolyticus  be- 
came rampant  in  the  wards.  The  streptococcus  compli- 
cations date  their  onset  at  some  time  during  these  two 
months. 

Table  LXT  shows  the  number  of  admissions  to  the  measles 
wards  by  weeks  and  the  patients  among  them  found  to  he 
carrying  hemolytic  streptococci.  It  also  shows  the  num- 
ber of  S.  hemolyticus  carriers  developing  each  week  among 
patients  under  treatment  in  the  "clean"  wards,  as  identi- 
fied by  throat  cultures  repeated  at  weekly  intervals.  For 
purposes  of  orientation,  the  number  of  cases  developing 
streptococcus  pneumonia  and  otitis  media  with  its  subse- 
quent mastoiditis  are  given  for  each  week  during  the  period 
of  observation. 

An  admission  to  the  measles  ward  can  generally  be  re- 
garded as  an  acute  case  of  measles.  There  are  a  few  ex- 
ceptions to  this  statement  and  these  are  cases  of  measles 
treated  in  barracks  and  afterwards  transferred  to  the  base 
hospital.  A  relatively  small  number  of  such  cases  fur- 
nished 1<>  of  the  cases  positive  for  hemolytic  streptococci 
on  admission  to  the  measles  ward. 

An  admission  to  the  measles  ward  does  not  indicate  ad- 
mission to  the  hospital,  because  a  considerable  number  of 


SECONDARY  INFECTION  IN  WARD  TREATMENT  03?  MEASLES    299 


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300      PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATOR'S   TRACT 

cases  of  measles  developed  from  time  to  time  among  pa- 
tients under  treatmenl  in  the  hospital  for  other  conditions. 
Since  these  patients  remained  in  other  wards  not  subjecl  to 
the  same  ward  management  and  with  no  distinction  be- 
tween those  positive  and  those  negative  for  hemolytic 
streptococci,  they  cannot  be  included  in  figures  to  show  the 
incidence  of  hemolytic  streptococci  in  patients  with  measles 
at  the  time  of  admission  to  hospital  from  the  cam]).  Two 
classifications  of  the  37  cases,  positive  when  first  observed, 
are  necessary. 

1.  Division  of  cases  according  to  days  in  the  hospital 
before  first   culture  was  taken : 

Days  in  Hospital  No.  of  cases 

0-1  (admission)  15  (2  not  acute) 

2-7  10 

More  than  7  12 

2.  Classification  according  to  stage  of  the  disease: 

During  acute  stage  21  cases 

After  acute  stage  16  cases 

The  first  classification  shows  only  13  cases  positive 
when  cultured  on  admission  to  the  hospital  and  also  during 
the  acute  stage  of  the  disease:  the  incidence  of  S.  hemolyti- 
cus  in  patients  on  admission  is  very  low  (1.7G  per  cent). 

The  second  classification  shows  a  slightly  higher  in- 
cidence for  cases  during  the  acute  stage  of  the  disease,  re- 
gardless of  whether  they  were  admitted  to  the  measles  ser- 
vice from  camp  or  from  another  service  of  the  hospital 
(2.4  per  cent).  These  findings  conform  with  those  at  Fort 
Riley  in  a  smaller  series  el'  cases  and  support  the  opinion 
that  the  hemolytic  streptococci  temporarily  disappear  from 
the  throat  during  the  acute  onset  of  measles.  Unfortu- 
nately controls  among  normal  men  in  Camp  Pike  were  not 
taken  at  intervals  throughout  the  period  of  three  months 
represented  by  this  study  of  measles,  but  all  controls  taken 
show  a  higher  incidence  than   that  found  among  measles 


SECONDARY  INFECTION  IN  WARD  TREATMENT  OF   MEASLES    30] 

patients  on  admissions  over  ;i  period  of  time  comparable  to 
that  of  the  control  series. 

The  gradual  increase  in  the  percentage  of  patients  de- 
veloping hemolytic  streptococci  in  their  throats  in  wards 
receiving  only  streptococcus  free  cases  demonstrates  that 
the  admission  culture  and  the  subsequent  weekly  cultures, 
with  the  separation  of  all  patients  ind'entified  as  carriers, 
did  not  suffice  to  control  the  spread  of  streptococcus  in  this 
group  of  cases.  It  is  interesting  to  note  that  the  greatesl 
incidence  of  streptococcus  carriers  among  these  patients 
occurred  three  weeks  after  the  height  of  the  measles  epi- 
demic, when  it  became  about  four  times  that  observed  at 
the  height  of  the  measles  epidemic.   . 

When  we  consider  the  time  relations  of  the  strepto- 
coccus complications,  it  is  noteworthy  that  they  begin  to 
appear  somewhat  after  the  appearance  of  streptococcus 
carriers  and  then  increase  parallel  with  the  increase  in  the 
numbers  of  carriers.  The  relative  number  of  complications 
developing  among  the  first  carriers  which  were  identified  is 
less  than  that  among  the  carriers  appearing  later.  This 
suggests  an  increase  in  virulence  of  hemolytic  streptococci 
attending  their  wider  dissemination. 

Tables  LXII  and  LXITI  are  introduced  for  the  purpose  of 
showing  to  what  extent  duration  of  stay  in  the  hospital 
increases  the  individual's  chances  of  acquiring  hemolytic 
streptococci.  Table  LXTI  includes  all  cases  admitted  to  and 
treated  in  the  measles  wards.  On  repeated  cultures,  prev- 
ious positives  and  negatives  were  cultured  alike  and  the 
total  positives  reported  for  each  week. 

Table  LXIII  includes  only  those  cases  treated  in  the 
"clean"  wards  and  known  to  be  negative  on  previous  cul- 
ture. 

A  comparison  of  Tables  LXII  and  LXIII  gives  some  indi- 
cation of  what  might  have  been  expected  if  the  carriers  had 
not  been  removed  from  the  treatment  wards  at  weekly  in- 
tervals.    "With  the  carriers  removed  from    the    "clean" 


302      PNEUMONIAS  a\'I>   [NFECTIONS  OF  RESPIRATORS  TRACT 


TAB]  E    I.  XI  I 

[NCIDF.nce  of  Hemolytic  Stki  ptococci  IX    Thkoats  OF  MEASLES  CASES  WITH 
Reference  to  Period  in  Hospital 

( All  cases  treated  in  the  wards ) 


P]  mod   IN 
MEASLES    WARD 


(Admission  i 

1  week 

2  weeks 
.".  weeks 
i  weeks 
5  weeks 
ii  weeks 

7  weeks 

8  weeks 

9  weeks 

10    Weeks 

]  1    weeks 


NO.    CASES 
(i  LTURED 


867 

768 

479 

240 

133 

82 

53 

25 

13 

it 

6 


Mi.    POSITIVE    FOR 

HEMOLYTIC 
STREPTO(  i"  I  i 


37 

si 

109 

63 

44 

26 

14 

8 

1 

1 

0 

0 


PKK    CEXT    POSITIVE 
FOB    EEMOLYTIC 

STREPTOCOCCI 


4.2 

10.9 
22.8 
26.2 

33.1 
31.7 

•_'<;.  i 
32.0 

7.7 
11.1 

0 

0 


Table  LXIII 

Weekly  Development  of  Hemolytic  Streptococci  in  Throats  of  Patients 
Treated  in  "Clean"  Wards 


period   in 
m  easles  "ward 

xo.  cases 
CULTURED 

NO.   POSITIVE 

FOR    HEMOLYTIC 

STREPTOCOCCI 

PER    CEXT    POSITIVE 

FOR   HEMOLYTIC 

STREPTOCOCCI 

1  week 

738 

67 

9.1 

2   weeks 

424 

74 

17.4 

3  weeks 

195 

34 

17.4 

4  weeks 

92 

16 

17.4 

5  weeks 

4fi 

7 

15.2 

6    weeks 

26 

4 

15.4 

7  weeks 

14 

3 

21.4 

8  weeks 

8 

0 



9  weeks 

5 

0 



10  weeks 

4 

0 



11  weeks 

3 

0 



cases  and  segregated  in  a  separate  ward  so  as  to  be  re- 
moved effectively  as  sources  of  spread  of  the  S.  hemolyti- 
cns  in  feci  ion  to  elcaii  cases,  the  percentage  incidence  with 
all  cases  considered  rose  to  a  point  nearly  twice  as  high 
as  that  ever  readied  in  the  wards  where  clean  cases  alone 
were  allowed  to  remain.  Had  these  carriers  not  been  sep- 
arated, and  remained  in  contact  with  cases  free  from  hemo- 
lytic streptococci,  they  would  have  served  as  jnst  so  many 
more  sources  of  infection,  and  an  incidence  of  at  least  twice 


SECONDARY  INFECTION   IN   WARD  TREATMENT  OP   MEASLES    303 

that  recorded  for  all  cases  combined,  or  Four-  limes  that 
of  the  treatment  wards,  might  have  been  expected.  These 
results  indicate  that  the  weekly  separation  of  carriers  from 
clean  cases  did,  to  a  considerable  extent,  lower  the  indi 
vidual's  danger  of  acquiring  S.  hemolyticus  infection 
while  in  the  hospital. 

Complications  of  Measles 

In  Table  LXIV  the  complications  developing  in  the  mea- 
sles patients  under  observation  at  Camp  Pike  are  tabulated. 
In  the  division  of  the  complications  developing  in  "carri- 
ers" and  "noncarriers"  of  the  hemolytic  streptococci,  ref- 
erence is  made  only  to  the  records  of  the  throat  cultures. 
The  division  is  therefore  not  dependent  upon  the  bacteriol- 
ogy of  the  complications.  For  example,  only  9  of  the  12  cases 
of  pneumonia  developing  in  ' '  carriers ' '  were  streptococcus 
pneumonias.  On  the  other  hand,  the  cases  of  mastoiditis 
following  otitis  media  were  almost  invariably  due  to  hemo- 
lytic streptococci.  Of  the  10  otitis  cases  occurring  in  "non- 
carriers,"  4  developed  mastoiditis  and  3  of  these  showed 
hemolytic  streptococci  on  culture  from  the  mastoid  cells 
at  operation.  Missed  cases  of  identification  of  S.  hemo- 
lyticus by  throat  culture  in  cases  which  develop  S.  hemo- 
lyticus complications  may  arise  from  a  number  of  causes. 
It  is  desired  here  only  to  direct  attention  to  these  dis- 
crepancies. 

Pneumonia  Following  Measles. — Fifty-six  cases  of  pneu- 
monia following  measles  occurred  during  the  period  of  ob- 
servation in  this  group  of  867  cases  of  measles.  Of  these, 
9  were  streptococcus  pneumonias.  This  gives  an  incidence 
for  streptococcus  pneumonias  of  1.04  per  cent,  while  that 
for  all  the  pneumonia  is  6.4  per  cent.  There  were  S  cases 
of  lobar  and  48  cases  of  bronchopneumonia.  Seventeen 
fatal  cases  occurred  giving  a  mortality  rate  of  30.4  per  cent 
for  the  group.     Five  of  these  fatal  cases  occurred  among 


304 


PX 


MONIAS  A\l>    IX  FEC 


i\: 


iPIRATORl'   TRACT 


Table  LXIV 

Complications  Developing  in  867  Cases  of  Measles  \t  Camp  Pike. 

Distribution  op  Complications  Between  242  "Carriers" 

and  625  "  noncarriers ' '  op  bemolytic  streptococci 

prow   septem  ber   15  to   i  '        cbeb    15,   1918 


NUMBER 

OCCURRING    IN 

PER 

CENT    IX 

NAME  OF 

-' 
-      - 

'  '  NONCARRIERS 
ill'  EEM.  STREP. 

IX  COM 
RD  OP 
LTURES 

- 
- 

— 

- 

Eh 
O 
Eh 

«  « 

•  OMPLICATION 

—  ~ 
r.   r. 

M 

—  _* 

—  & 

%  H 

CASKS  WITH 
PLETE  RECO 
PHROAT  CU 

w 

- 
< 

«  3 

.  - 

a  s 

H     - 

■-    !C 

as 

u  a 

S  w 
o  W 

?  fc 

»    o 

Pneumonia 

12 

44 

0 

56 

(5.4 

5.0 

7.0 

otitis  media 

:;i 

11 

6 

48 

5.5 

L2.8 

1.8 

Mastoidil  is    i  follow- 

ing otitis  media  i 

15 

4 

4 

23 

2.6 

6.2 

0.6 

Local  meningil  is    (ex 

tension    from     mas 

toid) 

•> 

0 

0 

0 

Frontal  sinusil  is 

1 

0 

H 

1 

Ethmoidal  sinusitis 

(i 

1 

n 

1 

Suppurative 

••nth  litis 

1 

i) 

o 

1 

(  'ervical  adenitis 

1 

0 

0 

1 

Acute  bronchitis 

4 

•> 

0 

6 

Acute  tonsillitis 

4 

1 

II 

.l 

Acute  laryngitis 

and  aphonia 

1 

i) 

1) 

1 

Acute  pleurisy 

2 

1 

(1 

3 

Erysipelas  of  face 

ii 

1 

(1 

1 

Epidemic    meningitis 

0 

1 

0 

1 

Note. — The  percentages  of  incidence  of  pneumonia  and  otitis  media  in 
the  "earner"  and  "noncarrier"  groups  are  at  direct  variance.  It  would 
appear  from  these  findings  thai  streptococci  very  readily  invade  the  middle 
ear  from  the  throat  and  set  up  grave  disorders.  The  invasion  of  the  lung 
from  the  throat  occurs  with  less  frequency.  Hemolytic  streptococci  perhaps 
never  initiate  the  pneumonic  processes  and  can  be  regarded  as  more  or  less 
accidental   secondary  invaders. 


the  9  streptococcus  pneumonias.  The  mortality  rate  for 
the  streptococcus  pneumonia  thus  was  55.5  per  cent;  thai 
for  the  nonstreptoeoccus  group  was  25.5  per  cent.  All  1) 
cases  of  streptococcus  pneumonia  developed  empyema.  In 
7  eases  it  was  diagnosed  clinically;  in  2  at  autopsy  only. 
No  eases  of  empyema  developed  in  the  group  of  nonstrepto- 
eoccus pneumonias. 


SECONDARY  INFECTION   IN  WAED  TREATMENT  OF  MEASLES    305 

The  relation  of  these  pneumonias  following  measles,  to 
the  influenza  epidemic  lias  been  discussed.  The  time  rela- 
tions between  the  onsets  of  measles  and  that  of  the  sub- 
sequent pneumonia  vary  widely.  There  appeaj-s  to  be 
nothing  constant  in  the  length  of  time  between  the  onset 
of  measles  and  that  of  the  pneumonia.  In  30  of  the  cases 
this  period  is  less  than  ten  days;  in  the  remaining  26  cases, 
it  ranges  from  ten  to  thirty -two  days  (Chart  4). 

In  the  ward  treatment  of  these  cases  of  pneumonia,  they 
were  divided  into  three  groups  according  to  their  clinical 
characters  and  according  to  the  results  of  throat  and 
sputum  cultures. 

(a)  Streptococcus  pneumonias  9  cases 

(b)  Pneumonia  with  hemolytic  streptococci  in 
the  throat  without  symptoms  referable  to 
the  streptococcus  13  cases 

(c)  Pneumococcus  pneumonias  not  carrying 
hemolytic  streptococci  34  cases 

The  streptococcus-free  cases  were  treated  in  a  separate 
ward.  Cases  were  admitted  to  this  ward  directly  from  the 
"clean"  measles  wards,  but  only  after  a  throat  culture 
taken  prior  to  their  transfer  had  been  negative  for  the 
hemolytic  streptococcus. 

The  other  two  groups  were  treated  together  in  another 
ward,  but  in  strictly  separate  compartments  of  it.  This 
precaution  was  carried  out  on  the  assumption  that  patients 
with  an  acute  streptococcus  pneumonia  were  real  sources 
of  danger  in  the  ward  because  of  a  heightened  virulence  of 
the  organism  causing  the  grave  symptoms.  The  pneumo- 
nias subsequently  developing  hemolytic  streptococci  in 
their  throats,  without  their  presence  modifying  the  course 
of  the  pneumonia,  came  to  be  regarded  as  being  in  the  same 
class  with  uncomplicated  cases  of  measles  carrying  hemo- 
lytic streptococci,  in  so  far  as  their  being  potential  sources 
of  danger  in  a  ward  is  concerned. 


, , i— — — ■ — > — ■ ■ — 

.  _■  __  —J . 4  • — 

1    ________  _____  —  — ' —  — 


10 


15 


10 


25 


30 


Chart  4. — Shows  the  time  interval  between  the  onset  of  measles  and  the  onset  of  the 
subsequent  pneumonia  in  the  56  cases  of  pneumonia  following  measles  at  Camp  Pike. 
Each  case  is  represented  by  one  of  the  small  blocks  measured  along  the  ordinate.  The 
onset  of  measles  in  all  eases  is  represented  by  the  line  at  the  extreme  left  of  the  chart. 
The  onset  of  pneumonia  in  each  ease  is  indicated  by  the  limit  of  the  block  marked  off  in 
days  to  the   right  of  this   line. 


SECONDARY   [INFECTION   IN   WAKD  TREATMENT  OE   MEASLES    307 

(a)  Streptococcus  Pneumonias. — Nine  cases  of  strepto 
coccus  pneumonia  developed.  Of  the  867  cases  of  measles 
studied,  242  showed  throat  cultures  positive  Tor  the  hemo- 
lytic streptococci  at  some  period  of  their  stay  in  the  hos- 
pital. It  appears  then  that  3.7  per  cent  of  the  patients 
carrying  hemolytic  streptococci  in  their  throats  developed 
streptococcus  pneumonia.  Thirty-seven  cases  had  positive 
throat  cultures  when  first  observed  on  admission  to  the 
measles  wards.  It  is  significant  to  note  that  not  a  single 
case  of  pneumonia  of  any  kind  developed  among  these 
cases. 

MEASLES    PNEUMONIA;     STREPTOCOCCUS    GROUP 

Case  98,  O.  McN.  Onset  of  measles,  Sep.  19 ;  admitted  to  hospital  Sep.  21 ; 
onset  of  bronchopneumonia,  Oct.  21 ;  of  empyema,  Oct.  23-  Recovered  from 
pneumonia ;  convalescent  in  empyema  ward. 

Bacteriology. — 1.  Throat  culture  for:  (a)  S.  hem.:  Sep.  21,  -;  28,  -;  Oct. 
9,  -;  20,  -;  23,  +;  Nov.  2,  -;9,  -;  15,  -;  (b)  B.  influenza;:  Sep.  21,  +;  28,  -; 
Oct.  9,  +.     2.  Pleural  fluid   (culture)   S.  hem-  Oct.  23,  +. 

Case  141,  J.  G.  G.  Autopsy  No.  438.  Onset  of  measles,  Sep.  28;  admitted 
to  hospital,  Oct.  1;  onset  of  bronchopneumonia,  Oct.  6;  of  otitis  media  (bilat- 
eral), Oct.  12;  died,  Oct.  18. 

Bacteriology. — 1.  Throat  culture  for:  (a)  S.  hem.,  Oct.  2,  -;  6,  -;  8,  -; 
(b)  B.  influenzas,  Oct.  2,  -;  6,  +;  8,  +.  2.  Autopsy  cultures:  Heart  blood,  neg- 
ative; left  lung,  Pneumococcus  II  atypical,  B.  influenzae  and  S.  viridans;  right 
lung,  S.  hem.  and  B.  influenzas ;  right  bronchus,  S.  hem.  and  B.  influenzae. 

Case  147,  S>.  W.  Autopsy  No.  442.  Onset  of  measles,  Oct.  1;  admitted  to 
hospital,  Oct.  2;  onset  of  bronchopneumonia,  Oct.  17,  with  chill  and  rapid 
development;  died,  Oct.  18. 

Bacteriology. — 1.  Throat  culture  for:  (a)  S.  hem.,  Oct  2,  -;  9,  -;  15,  -; 
18,  +;  (b)  B.  influenzas,  Oct.  2,  -;  9,  -;  15,  -;  18,-.  2.  Autopsy  cultures: 
Heart  blood,  S.  hem. ;  right  main  bronchus,  S.  hem.  and  B.  influenzae. 

Case  281,  T.  M.  Onset  of  measles,  Oct.  6 ;  admitted  to  hospital  Oct.  9 ;  on- 
set of  bronchopneumonia,  Oct.  21 ;  of  empyema,  Oct.  23 ;  recovered  from  pneu- 
monia ;  convalescent  in  empyema  ward. 

Bacteriology— -1.  Throat  culture  for:  (a)  S,  hem.,  Oct.  10,  -;  20,  -;  24,  +; 
Nov.  2,  +;  9,  +;  15,  +  ;  (b)  B.  influenza-,  Oct.  10,  -;  20,  +.  2.  Culture  from 
pleural  fluid,  Oct.  23,  S.  hem. 

Case  285,  J.  H.  Onset  of  measles,  Oct.  4;  admitted  to  hospital,  Oct  9; 
onset  of  lobar  pneumonia,  Oct.  29 ;  of  empyema,  Nov.  9 ;  convalescent  in  em- 
pyema ward. 

Bacteriology. — 1.  Throat  cultures  for:  (a)  S.  hem.,  Oct.  11,  -;  20,  -;  24, 
+  ;  29,  -;  Nov.  2,  -;  9,  -;  (b)  B.  influenza?,  Oct.  11,  -.  2.  Cultures  from  pleu- 
ral fluid,  Nov.  9  and  13,  S.  hem. 


308      PNEUMONIAS  AXP   [NFECTIONS  or  RESPIRATORY  TRACT 

Case  714,  W.  II.  Onsel  of  measles,  Oct.  26;  admitted  to  hospital,  Oct.  28; 
otitis  media,  Noy:  s:  onset  of  bronchopneumonia,  Nov.  9;  of  empyema,  Nov. 
17:  convalescent  in  pneumonia  ward. 

Bacteriology— 1.  Throat  culture's  for:  S.  hem.,  Oct.  28,  -;  Nov.  4,  -;  12,  +; 
23,  :  30,  :  ;  Dec.  7,  ;  12,  .  2.  Sputum:  Nov.  L0,  Pneumococcus  11  atypical, 
S.  hem.  and  r>.  influenza}. 

Case  730,  W.  S.  Autopsy  No.  491.  Onset  of  measles,  Oct.  26;  admitted  to 
hospital,  Oct.  29;  onset  of  bronchopneumonia,  Nov.  10;  of  empyema,  Nov.  11; 
of  cervical  adenitis,  Nov.  5;  (lied,  Nov.  15. 

Bacteriology.— 1.  Throat  culture  for:  S.  hem.,  Oct.  30,  -;  Nov.  4,  +.  2. 
Sputum:  Nov.  10,  S.  hem.  •"..  Pleural  fluid:  Nov.  11.  S.  hem.  Autopsy  bac- 
teriology: Heart  Mood,  S.  hem.;  right  main  bronchus,  V>.  influenza?,  B.  eoli ; 
right  lung,  S.  hem.  and  B.  influenza;;  right  pleura,  S.  hem.;  peritoneum,  S.  hem. 

Case  751,  P.  B.  Autopsy  No.  492.  Entered  hospital,  Oct.  19;  onset  of 
measles,  Oct.  .'!(l;  of  bronchopneumonia,  Nov.  5;  of  right  empyema,  Nov.  12; 
died,  Nov.  16. 

Bacteriology. — 1.  Throal  cultures  for:  S.  hem.,  Nov.  1,  -;  4,  +  ;  15,  +. 
2.  Sputum:  Nov.  13,  B.  influenza?  and  S.  hem.  3.  Autopsy  cultures:  Heart 
blood,  S.  hem.;  right  lung,  S.  hem.,  Pneumococeus  IV,  B.  influenza?,  B.  coli; 
pericardium,  negative;  right  pleura,  S.  hem.;   peritoneum,  S.  hem. 

Case  S80,  B.  McN.  Autopsy  No.  507.  Onset  of  measles,  Nov.  30;  entered 
hospital,  Dec.  3;  onset  of  bronchopneumonia,  Dee.  11;  of  empyema,  Dec.  14; 
died,  Dec.  14. 

Bacteriology. — 1.  Throat  cultures  for:  S.  hem.,  Dec.  3,  -;  5,  -;  12,  +. 
2.  Cultures  from  pleural  fluid,  Dec.  14,  S.  hem.  ?>.  Autopsy  cultures:  Heart 
blood,  S.  hem.;  right  main  bronchus,  S.  hem.,  B.  influenza?,  staphylococcus  (a 
few)  ;  left  lung,  S.  hem. ;  left  pleura,  S.  hem. 

The  average  period  in  the  hospital  before  the  develop- 
ment of  the  streptococcus  pneumonia  is  about  two  weeks. 
Cases  98  and  285  were  in  the  hospital  thirty  and  twenty 
days  respectively  before  the  onset  of  pneumonia.  There 
is  a  record  of  from  one  to  four  negative  throat  cultures 
on  each  ease  before  streptococcus  was  found  in  the 
throat.  This  enables  us  to  fix  the  onset  of  the  pneumonia 
with  reference  to  the  appearance  of  the  streptococcus  in 
the  throat. 

Case  141  stands  alone  as  representing  a  class  in  which 
S.  liemolyl  ieus  was  implanted  upon  a  pneumoeoecus  pneu- 
monia during  its  course.  In  this  instance  two  throat  cul- 
tures on  alternate  days  after  the  onset  of  the  pneumonia 
wen-  negative   for  hemolytic  streptococci.    Unfortunately 


SECONDARY  INFECTION  IN  WARD  TREATMENT  OF   MEASLES    309 

the  last  record  of  a  throat  culture  is  for  one  taken  ten  days 
before  the  fatal  termination  of  the  case,  and  it  can  only 
he  stated  that  the  S.  hemolytieus  infection  was  implanted 
within  the  last  ten  days  of  the  course  of  the;  pneumonia, 
perhaps  on  or  about  October  12  when  bilateral  otitis  media 
developed. 

In  Cases  285  and  730  hemolytic  streptococci  were  found 
in  the  throats  five  and  six  days  respectively  before  the  onset 
of  pneumonia.  They  represent  the  2  cases  of  pneumonia 
which  developed  in  patients  isolated  in  the  streptococcus 
"carrier"  ward.  Case  285  is  of  particular  interest  for 
several  reasons.  It  is  the  only  case  of  lobar  pneumonia 
in  the  group  and  happens  also  to  be  the  only  case  from 
which  B.  influenzas  was  not  obtained.  S.  hemolytieus  was 
found  only  once  on  throat  culture,  i.  e.,  five  days  before  the 
onset  of  the  pneumonia.  Three  throat  cultures  after  the 
onset  of  the  pneumonia  were  negative.  The  case  ran  the 
course  of  a  lobar  pneumonia.  Eleven  days  after  the  onset 
(November  9)  a  small  amount  of  pleural  fluid  was  diag- 
nosed. Aspirated  fluid  on  this  date  and  again  four  days 
later  showed  many  streptococci  in  smears  and  pure  cultures 
of  S.  hemolytieus. 

The  remaining  6  cases  belong  to  a  group  in  which  hemo- 
lytic streptococci  were  first  identified  in  the  throats  after  the 
cases  had  been  reported  to  the  laboratory  as  pneumonia  sus- 
pects to  be  examined  by  culture  before  transfer  from  the 
measles  ward.  In  all  these  cases  the  culture  taken  at  this 
time  was  positive  while  all  cultures  taken  before  were  nega- 
tive. In  some  cases,  e.  g.,  Cases  98,  147,  and  281,  throat 
cultures  taken  only  one  or  two  days  before  the  onset  of  the 
pneumonia  were  negative.  In  these  cases  the  onset  of  the 
pneumonia,  and  the  appearance  of  the  streptococcus  in  the 
throats  appear  to  be  simultaneous. 

It  should  be  noted  that  the  period  between  the  appearance 
of  the  hemolytic  streptococci  in  the  throat  and  the  develop- 
ment of  the  pneumonia  is  very  short  in  all  cases.     In  this 


.'!1D      PNEUMONIAS  A\H   INFECTIONS  OF   RESPIRATOR'S   TRACT 

small  group  of  cases  S.  hemolyticus  infection  which  lias 
complicated  pneumonia  lias  been  acquired  at  <>r  near  the 
lime  of  onset  of  the  pneumonia. 

( b )  Pneumonia  with  Hemolytic  Streptococci  in  the 
Throat  without  Symptoms  Referable  to  the  Streptococcus. 
—Thirteen  cases  of  pneumonia  associated  with  measles  de- 
veloped into  S.  hemolyticus  "carriers."  without  having  the 
course  of  the  disease  affected  by  the  presence  of  the  organ- 
ism in  the  throat.  Cases  705,  STL',  and  1SS  are  of  interest 
in  that  hemolytic  streptococci  were  identified  in  the  throats 
from  one  to  six  days  prior  to  the  onset  of  the  pneumonia. 
Tn  spite  of  their  presence,  the  symptoms,  course  and  out- 
come of  the  pneumonia  were  apparently  unaffected.  One 
of  these  cases  (Case  872)  died.  Autopsy  showed  lobar 
pneumonia  with  no  signs  of  invasion  of  the  lung  by  hemo- 
lytic streptococci.  Cultures  at  autopsy  showed  thai  pneu- 
monia was  duo  to  a  pneumococcus,  Type  II  atypical.  A 
few  hemolytic  streptococci  were  found  in  culture  from  the 
right  main  bronchus. 

Of  the  remaining  10  cases  1  developed  S.  hemolyticus 
in  a  throat  culture  at  the  end  of  the  first  week  of  the  pneu- 
monia; 3  during-  the  second  week;  1  during  the  third  week, 
and  5  farther  along  in  the  convalescent  period.  Tn  8  cases 
hemolytic  streptococci  appeared  in  the  throat,  at  a  time 
when  invasion  of  the  lower  respiratory  tract  by  the  strep- 
tococcus might  he  expected,  and  yet  none  of  them  developed 
evidence  of  streptococcus  pneumonia.  The  f)  cases  with 
hemolytic  streptococci  appearing  late  in  convalescence  are 
not  of  particular  interest,  since  the  dangers  of  lower  res- 
piratory invasion  are  much  reduced  after  the  acute  stag*' 
of  the  pneumonia  has  passed.  Three  of  these  cases  (Cases 
078,  ~'1~)  and  31)8)  did  however  develop  ear  complications 
directly  referable  to  the  streptococcus  invasion  of  the 
throat.  Two  of  them  terminated  in  mastoiditis  with  op- 
eration. These  cases  emphasize  the  greater  tendency  of  S. 
hemolyticus  to  invade  the  middle  ear  rather  than  the  lung. 


SECONDARY  INFECTION  IN   WAIU)  TUEATMEXT   OF    .MEASLES    .'}  1  1 

In  3  fatal  cases  of  pneumococcus  pneumonia  in  which  dur 
ing  life  no  hemolytic  streptococci  were  found  by  throal  cul- 
ture, a  few  hemolytic  streptococci  were  round  at  autopsy 
in  culture  from  the  main  bronchi,  along  with  predominating 
growths  of  pneumococci  and  B.  influenzae.  In  2  instances 
there  was  frank  lobar  pneumonia  and  in  the  third  broncho- 
pneumonia; there  was  no  evidence  to  show  that  hemolytic 
streptococci  had  airy  relation  to  the  pneumonia  which  was 
found. 

MEASLES    PNEUMONIAS;    GROUP    CARRYING    HEMOLYTIC    STREPTOCOCCI 

Case  705.  Onset  of  measles,  Oct.  25;  admitted  to  hospital,  Oct.  27;  onset 
of  bronchopneumonia,  Nov.  10;  acute  pleurisy,  Nov.  16;  convalescent  in  pneu- 
monia ward. 

Bacteriology. — 1.  Throat  cultures  for:  S.  hem.,  Oct.  27,  -;  Nov.  4,  -;  11, 
+  ;  15,  +  ;  23,  -;  30,  -;  Dec.  7,  -;  12,  -.  2.  Sputum:  Nov.  10,  Pneumococcus  II 
atypical,  S.  hem.  and  B.  influenzae. 

Case  872.  Autopsy  No.  508.  Onset  of  measles,  Nov.  29;  admitted  to  hos- 
pital, Nov.  30 ;   onset  of  lobar  pneumonia,  Dec.  10 ;   died,  Dec.  14. 

Bacteriology. — 1.  Throat  cultures  for:  S.  hem.,  Nov.  30,  -;  Dec.  5,  +; 
10,  +;  12,  +;  14,  +.  2.  Autopsy  culture:  Heart  blood,  Pneumococcus  II  atyp- 
ical; right  main  bronchus,  Pneumococcus  II  atypical,  B.  influenzae,  S.  hem.  (a 
few);  left  lung,  Pneumococcus  II  atypical;  left  pleura,  Pneumococcus  II 
atypical. 

Case  1SS.  Onset  of  measles,  Oct.  3 ;  admitted  to  hospital,  Oct.  4 ;  onset  of 
bronchopneumonia,  Oct.  14;  recovered  and  discharged  from  hospital,  Nov.  24. 

Bacteriology. — 1.  Throat  cultures  for:  (a)  S.  hem.,  Oct.  5,  -;  8,  +;  12,  +; 
19,  +;  20,  +;  27,  -;  Nov.  2,  -;  9,  4;  15,  -;  (b)  B.  influenzas,  Oct,  5,  -;  8,  -; 
12,  +;  19,  +. 

Case  678.  Onset  of  measles,  Oct.  23;  admitted  to  hospital,  Oct.  25;  onset 
of  bronchopneumonia,  Nov.  2 ;  of  otitis  media,  Nov.  9 ;  of  mastoiditis,  Nov. 
13 ;  mastoid  operation,  Nov.  20 ;  still  under  treatment. 

Bacteriology. — 1.  Throat  cultures  for:  S.  hem.,  Oct.  25,  -;  Nov.  4,  -;  5,  -; 
12,  +.  2.  Sputum:  Nov.  3,  Pneumococcus  Type  IV,  and  B.  influenza?.  3.  Cul- 
ture from  mastoid  bone  at  operation,  Nov.  20,  S.  hem. 

Case  389.  Admitted  to  hospital,  Oct.  2,  with  diagnosis  of  influenza;  onset 
of  bronchopneumonia,  Oct.  7;  onset  of  measles,  Oct.  13;  phlebitis  (right  leg), 
Oct.  22 ;  otitis  media,  Oct.  31 ;  recovered. 

Bacteriology. — 1.  Throat  cultures  for:  (a)  S.  hem.,  Oct.  16  -;  20,  -:  27,  4; 
Nov.  2,  +;  9,  +;  15,  -;  23,  -;  30,  -;  Dec.  7,  -;  12,  -;  (b)  B.  influenzae,  Oct. 
16,  -. 

Case  725.  Onset  of  measles,  Oct.  IS;  one  week  in  measles  barracks;  ad- 
mitted to  hospital,  Oct.  27;  onset  of  lobar  pneumonia,  Oct.  23;  otitis  media, 
Nov.  7;  mastoid  operation,  Nov.  20;  still  under  treatment. 


312      PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATOR'S   TRACT 

Bacteriology. — 1.  Throat  cultures  for:  (a)  S.  hem.,  Oct.  29,  -;  Nov.  1,  -; 
5,  -:  12.  +:  (6.)  B.  influenzae,  Oct.  29,  +.  2.  Sputum:  Nov.  2,  Pneumococcus 
II  atypical.  B.  influenzae.  •"■.  Culture  from  mastoid  at  operation,  Nov.  20, 
S.  hem. 

(c)  Pneumococcus  Pneumonias  not  Carrying  Hemolytic 
Streptococci.  Thirty-four  cases  of  pneumonia  following 
measles  wcnl  through  their  entire  course  iii  the  hospital 
with  no  throat  culture  positive  for  hemolytic  streptococci. 
In  some  of  these  cases  there  are  records  of  twelve  negative 
throat  cultures.  Eleven  fatal  cases  occurred  in  this  group. 
Autopsy  findings  and  bacteriology  showed  in  each  instance 
that  S.  hemolyticus  was  not  the  cause  of  the  pneumonia. 

Measles  During  the  Course  of  Pneumonia.  Eleven  cases 
of  pneumonia  which  developed  measles  during  the  course 
of  the  pneumonia  came  under  observation.  Hemolytic 
streptococci  appeared  in  the  throats  of  3  of  these  patients 
during  convalescence,  but  there  was  no  evidence  that  it  in- 
vaded the  lung.  In  one  fatal  ease  autopsy  showed  that 
there  was  no  streptococcus  pneumonia;  pneumonia  followed 
influenza  and  the  onset  of  measles  occurred  three  days  after 
the  onset  of  bronchopneumonia. 

Bacteriology  of  Pneumonia  Following  Measles. — When 
observations  made  during  life  are  combined  with  the  results 
of  postmortem  cultures,  the  bacteriology  of  35  of  the  56 
cases  is  available  and  is  as  follows:  Pneumococcus  Type  II 
atypical  in  36  per  cent,  Type  IV  in  22.9  per  cent,  Type  I  in 
2.8  per  cent,  Type  III  in  2.8  per  cent,  hemolytic  streptococci 
in  22.4  per  cent,  and  B.  influenzae  in  88.6  per  cent  of  these 
cases. 

Otitis  Media  and  Mastoiditis  Complicating  Measles. — The 
occurrence  of  otitis  media  and  mastoiditis  complicating 
measles  in  patients  harboring  hemolytic  streptococci  in 
their  throats  has  already  been  presented  (Table  LXTV). 
The  bacteriology  of  these  complications  was  not  studied 
by  this  commission.  The  records  of  the  base  hospital  lab- 
oratory at  Camp  Tike  contain  reports  of  twenty-nine  cul- 
tures made  at  operation   from  pus  in  the  middle  ear  and 


SECONDARY  INFECTION"  IN  WARD  TREATMENT  OF   MEASLES    313 

the  mastoid  bone.  Hemolytic  streptococci  were  found  in 
22  of  these  cases.  Throat  culture's  were,  in  accord  with 
these  positive  findings  in  all  except  a  few  instances.  The 
throat  culture  serves  as  a  fairly  reliable  index  of  the  bac- 
terial nature  of  these  complications.  By  combining  our 
records  of  throat  cultures  with  the  results  of  the  cultures 
from  the  lesions,  hemolytic  streptococci  were  obtained  from 
37  of  the  48  cases  of  otitis  media.  In  23  cases  of  mastoditis 
following  the  otitis  media,  hemolytic  streptococci  were  dem- 
onstrated in  all  except  2.  It  is  evident  that  the  great  ma- 
jority of  these  complications  were  due  to  hemolytic  strep- 
tococci. 

The  relation  between  the  appearance  of  hemolytic  strep- 
tococci in  the  throat  and  the  onset  of  the  otitis  is  recorded 
in  all  except  4  of  the  31  instances  of  otitis  media  occurring 
in  patients  with  throat  cultures  positive  for  hemolytic 
streptococci.  These  four  patients  had  positive  throat  cul- 
tures when  first  observed  and  represent  the  only  patients 
who  carried  hemolytic  streptococci  when  admitted  to 
measles  wards  and  developed  complications. 

The  first  of  these  patients  had  been  under  treatment  in 
an  otologic  ward  during  a  month  before  measles  developed. 
Measles  caused  a  recurrence  of  disease  of  the  ear  with 
double  mastoiditis  requiring  bilateral  ox^eration.  Two 
other  patients  had  been  in  the  hospital  ten  and  eleven  days 
respectively  before  they  were  admitted  to  the  measles 
ward;  on  admission  to  the  ward  otitis  media  was  present 
in  one  patient  and  in  the  other  it  developed  six  days  later. 
The  fourth  patient  was  admitted  to  the  measles  wards  di- 
rectly from  the  camp,  and  culture  from  the  throat  on  the 
day  of  admission  showed  the  presence  of  S.  hemolyticus. 
Two  weeks  later  at  the  time  of  onset  of  otitis  media,  culture 
from  the  throat  contained  no  hemolytic  streptococci.  Re- 
peated cultures  during  the  next  three  weeks  were  negative. 
No  complications  of  otitis  media  developed  and  no  direct 
cultures  from  the  ear  are  recorded. 


314      PNEUMONIAS  AND   INFECTIONS  OF  RESPIRATOR"?  TRACT 


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SECONDARY  INFECTION  IN  WAED  TREATMENT  OF  MEASLES    315 

Iii  this  series  of  cases  (Chart  5)  the  appearance  of  S. 
hemolyticus  in  the  throat  and  the  onset  of  otitis  media  are 
very  closely  associated  in  those  patients  in  whom  further 
extensions  of  the  streptococcus  infection  occurred.  In  in- 
stances in  which  appearance  of  streptococci  and  of  otitis 
media  are  separated  by  an  interval  of  more  than  seven  days, 
no  further  extension  occurred.  In  8  cases  in  which  this  in- 
terval is  seven  days  or  less  there  has  been  no  further  ex- 
tension of  the  infection. 

The  Dissemination  of  Hemolytic  Streptococci  in  Wards 

Beginning  October  24  cultures  for  the  identification  of 
carriers  of  hemolytic  streptococci  were  made  from  all  pa- 
tients in  a  ward  and  repeated  at  intervals  of  one  week. 
Prior  to  this  time  individual  patients  had  been  examined  at 
intervals  of  one  week,  so  that  an  entire  ward  was  never 
studied  on  any  particular  day.  This  system  did  not  iden- 
tify and  remove  all  "carriers"  in  a  ward  at  a  given  time 
and  was  abandoned  because  it  failed  to  show  the  conditions 
present.  Investigation  of  wards  as  units  proved  much 
more  satisfactory. 

The  studies  made  in  four  of  the  double  wards  used  for 
the  care  of  patients  with  measles  are  presented  in  Table 
LXV.  During  the  time  of  this  study  hemolytic  streptococci 
were  more  prevalent  than  at  an  earlier  period. 

Cultures  from  the  throats  of  all  patients  entering  these 
wards  were  negative  for  S.  hemolyticus  on  admission.  The 
table  showing  the  incidence  of  " carriers"  of  hemolytic 
streptococci  each  week  in  these  wards  demonstrates : 

1.  The  separation  of  "carriers"  and  "rionearriers"  by 
throat  culture  made  on  admission  does  not  prevent  the  in- 
crease of  streptococcus  "carriers"  in  wards. 

2.  Removal  of  all  "carriers"  found  by  cultures  on  ad- 
mission and  at  weekly  intervals  is  inadequate. 


316      PNEUMONIAS  A  X  I  >   [NFECTIONS  OF   RESPIRATORS  TRACT 


Table  LXV 
Ward  Conditions  with  Reference  to  Hemolytic  stkki'toi'ixvi-s  Infection 


•' 

^ 

-    - 

- 

w 

COMPLICATIONS 

-- 

g'fcj 

H    H 

15   H   Eh 

ASSOCIATED    WITH 

2  - 

-:  E*   - 

:-     • 
•   v.   S 

g   >   CD 

"    /.    P: 

HEM.    STREP.    WITH 
DATES    OF    OXSET 

REMARKS 

c  --  ■ 

=    C    | 

w   r  - 

ZiU 

ZhH 

i.  i.  - 

Ward  57 
11-3 

11-10 
11-17 

Ward  58 
11-3 

11-10 
11-17 


Ward  49 

10-25 

11-] 

11-8 

11-15 

11-22 

Ward  f)0 
in  25 
11-1 
11-8 
11-15 
1 1  -22 

Ward  41 
10-28 

11 -4 

11-11 

Ward 

11-21 

11-28 

12-5 

12-12 


Ward    12 


10-28 

11-4 

Ward 

10-21 

11-28 

12-5 

12-12 


35 

1 

13 

2 

16 

6 

7 

38 

11 

4 

6 

o 

37 

7 

31 

3 

35 

9 

32 

18 

in 

7 

29 

o 

43 

o 

32 

3 

20 

11 

11 

0 

-1.1 

4 

34 

9 

12 

8 

closed 

—No 

13 

0 

8 

4 

12 

4 

4 

3 

90 

0 

43 

7 

•losed 

—No 

16 

4 

12 

1 

20 

10 

14 

7 

2.8 
15.5 
37.5 


is.  I 
36.4 
33.0 


18.9 

9.7 

25.7 

56.3 

43.8 


3.4 
4.6 

9.4 
55.0 
0.0 


8.9 

26.5 
66.6 
pal  Lents. 
0.0 
50.0 
33.3 
75.0 


0 
16.3 
pal  tents. 
25.0 
12.5 
50.0 
.-.ii.ii 


None 


Otitis   media  : 
11-8     1   ease 
.11-7     1   ease 


Otitis  media 
10-2.1  2 
10-26 
10-28 
11-15 
11-18 
11-27 


rases 

case 

ease 

case 

ease 

case 


Otitis    media  : 

11-8  1  case 
11-13  1  ease 
11-22     1  case 


si  reptococeus 

in i hi ia  : 
(11-9       1 
11-10     1 
Otitis   media: 


L0-29 
11-4 
11-5 
11-11 

11-27 
1  2  3 


pneu- 

case) 
case 

ease 

case 

ease 

case 

case 
ease 


Streptococcus 

I uinonia : 

11-10      1 
12-11      1 

Otitis  media  : 
10-29  1 
1 2-3  1 
12-6       1 


ease 
case 

case 
case 
case 


Wards  .".7  and  58 
served  by  same 
ward  staff. 

Members  of  staff  cul- 
tured on  11-5,  11-12 
and  11-19. 
No  positives 


Wards  49  and  50 
served  by  same 
ward  staff. 

Ward   staff  cultured  : 
11-5        1  posit  i\  e 
11-12     1  positive 
11-26     2  positives 


Case  of  pneumonia 
developing  on  11-9 
was  transferred  to 
the  "clean"  pneu- 
monia ward  without 
a  throat  culture  to 
warrant  its  trans- 
fer; last  cull  ii re 
1 1-4  negative ;  cul- 
ture 11-12  in  pneu- 
monia ward  posi- 
tive 


Wards   4  1    and     12 
served  by  same 
ward    staff. 

Ward    staff    cult  lired 

1  1  5  2  posil  ive 

11-12  2  positive 

11-20  2  posil  ive 

12-2  1  positive 


SECONDARY  INFECTiON  IN  WARD  TREATMENT  OF  MKASI.KS    .'117 


Table  LXV — (Concluded) 


Ward  59 

SI  reptococeus 
pneumonia  : 

The  '■'<  cases  of  si  rep 
tococcus  pneumonia 
acquired  S.  hemoly- 

10-24 

37 

6 

16.2 

10-17     1  ease 

1  Lcus  infection  while 

10-31 

27 

5 

18.5 

10-21     1  case 

patients    in    the    16 

11-7 

9 

3 

33.3 

10-29     1  case 

bed     south     section 

11-12 

7 

1 

14.3 

( Mitis  media : 

11-1       1  case 

of   this    ward 
Case    developing    10- 

29  was  removed 
from  section  a  few 
days  before  onset 
of  pneumonia 

Ward  60 

Wards  59  and  60 

Streptococcus 

served  by  same 

pneumonia : 

ward   staff. 

10-24 

22 

1 

4.5 

10-21     1  case 

Ward  staff  cultured: 

10-31 

17 

2 

11.7 

Otitis  media  : 

11-5       0  positive 

11-7 

8 

1 

12.5 

10-31     1  case 

11-12     1  positive 

11-12 

6 

1 

16.6 

11-19     0  positive 

When  the  streptococcus  complications  are  traced  hack  to 
the  wards  in  which  the  streptococcus  infection  of  the  throat 
was  acquired,  it  is  found  that  with  the  exception  of  Case 
141  (already  cited)  all  the  streptococcus  pneumonias  arose 
from  two  double  wards.  Wards  41  and  42  furnished  4 
cases  at  times  when  streptococcus  was  rampant  in  them  and 
3  of  these  cases  arose  within  a  period  of  a  few  days. 
Wards  59  and  60  furnished  4  cases,  very  closely  associated. 
In  3  cases  the  streptococcus  infection  was  acquired  in  a 
section  of  Ward  59  containing  16  beds.  These  patients 
were  in  beds,  of  which  the  positions  are  represented  by  num- 
bers 2,  5,  and  7,  along  one  side  of  the  ward.  The  fourth 
instance  of  pneumonia  appeared  at  the  same  time  in  Ward 
60,  which  was  attended  by  the  same  ward  personnel,  but 
no  other  connection  can  be  established  between  this  case 
and  the  other  three. 

The  otitis  media  appeared  in  patients  scattered  through- 
out those  wards  for  measles  in  which  the  weekly  incidence 
of  "carriers"  was  rising  rapidly.  This  relation  is  illus- 
trated by  Wards  58,  50,  and  41.  The  same  observation  ap- 
plies to  streptococcus  pneumonia  arising  in  Wards  41  and 
42.  In  Ward  41  the  weekly  percentage  of  carriers  are 
October  28,  8.9,  November  4,  26.5  and  November  11,  66.6. 


318      PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATOR?  TRACT 

On  November  9  and  10  tin'  first  2  cases  <>f  streptococcus 
pneumonia  arising  Prom  this  ward  developed.  At  the  same 
time,  November  ML  a  third  case  appeared  in  another  part 
el'  this  same  ward  unit  (Ward  42)  where  the  spread  of 
hemolytic  streptococci  had  been  very  active.  These  ob- 
servations suggesl  thai  hemolytic  streptococci  may  build 
up  its  virulence  as  the  result  of  rapid  dissemination  to 
such  a  degree  that  it  is  capable  of  causing  grave  compli- 
cations. 

The  relation  of  complications  to  "carriers"  iu  Wards 
59  and  60  is  different  from  that  in  the  wards  just  cited. 
Wards  59  and  60  were  opened  on  October  9  and  before  Oc- 
tober 17;  when  the  first  case  of  fulminating  streptococcus 
pneumonia  occurred,  only  three  "carriers"  bad  been  found 
in  them.  From  October  17  to  24  when  tbe  record  in  Table 
LXV  begins  eight  "carriers"  were  removed.  Tbe  appear- 
ance of  a  ease  of  severe1  streptococcus  pneumonia  in  an 
unusually  clean  ward  was  followed  by  tin1  rapid  develop- 
ment of  "carriers,"  and  tin1  appearance  within  twelve  days 
of  3  other  cases  of  streptococcus  pneumonia,  2  of  which 
were  in  beds  close  to  the  first  case.  This  sequence  suggests 
focal  dissemination  of  a  streptococcus  from  a  case  in  which 
it  bad  suddenly  assumed  high  virulence. 

An  outbreak  of  infection  with  S.  hemolyticus  was  recog- 
nized on  November  12  in  a  measles-pneumonia  ward  which 
bad  been  opened  for  several  weeks  and  bad  continued  free 
from  streptococcus.  In  three  patients  hemolytic  strepto- 
cocci were  found  by  throat  cultures.  Inquiry  revealed  that 
a  nurse  in  tbis  ward,  recognized  as  a  streptococcus  "car- 
rier" tbe  week  before,  bad  been  retained  on  duty.  Two 
patients  well  advanced  in  tbe  course  of  their  pneumonias, 
bad  acquired  S.  hemolyticus  demonstrated  by  throat  ex- 
amination. Both  patients  developed  otitis  media  with  mas- 
toid extension  requiring  operations.  Cultures  from  both 
at  operation  showed  hemolytic  streptococci. 


SECONDARY   INDUCTION   IN    WARD  TREATMENT  OF   MEASLES    319 

The  third  patient,  with  acute  pneumonia,  had  been  sent 
into  the  ward  on  November  11  from  Ward  42,  which  a1  the 
time  was  a  highly  infected  ward;  no  culture  of  the  throal 
was  made  before  transfer.  This  patient  developed  strepto- 
coccus pneumonia  with  empyema  requiring  subsequent  op- 
eration. 

Discussion. — At  Camp  Funston,  where  the  prevalence  of 
S.  hemolyticus  in  the  measles  wards  did  not  rise  above  that 
among  normal  men  in  the  camp  at  large,  112  consecutive 
eases  of  measles  were  treated  without  a  single  complication 
due  to  hemolytic  streptococci. 

At  Camp  Pike,  the  investigation  began  at  the  onset  of 
a  small  epidemic  of  measles  at  a  time  when  hemolytic  strep- 
tococci were  an  almost  neglible  factor.  The  epidemic  of 
measles  was  followed  throughout  its  course;  and,  with  the 
passing  of  the  epidemic,  there  was  an  increase  in  the  prev- 
alence of  hemolytic  streptococci  which  assumed  alarming 
importance  in  the  production  of  complications. 

The  epidemic  of  measles  was  in  part  superimposed  upon 
the  epidemic  of  influenza,  so  that  deductions  concerning 
complications  strictly  due  to  measles  became  impossible. 
It  is  evident  that  influenza  pla3^ed  a  considerable  part  in 
producing  the  complications  of  measles  at  Camp  Pike. 

The  dissemination  of  hemolytic  streptococci  through 
measles  wards  was  controlled  only  in  part  by  the  methods 
used.  This  partial  control  may  have  served  to  limit  the 
incidence  of  streptococcus  pneumonia,  nine  instances  oc- 
curring among  867  cases  of  measles. 

In  the  ward  treatment  of  measles  effort  should  be  di- 
rected to  prevent  the  exposure  of  patients  free  from  hemo- 
lytic streptococci  to  S.  hemolyticus  "carriers."  By  this 
means  the  rate  of  development  of  S.  hemolyticus  "car- 
riers ' '  may  be  reduced. 

Measures  which  should  be  adopted  are  as  follows : 

1.  Adequate  wards  should  be  prepared  in  advance  for 
the  treatment  of  measles.  The  rather  gradual  onset  of 
epidemics  of  measles  makes  this  provision  possible. 


320      PNEUMONIAS  A\l>   IXI'I'.i  ITIONS  OF   RESPIRATOR'S   TRACT 

2.  The  separation  of  S.  liemolyticus  "carriers"  Prom 
other  patients  should  be  enforced.  Observation  wards, 
where  stricl   technic   to   prevent   transfer  of   infection   is 

practiced  and  where  throal  cultures  arc  made  on  admission, 
are  essential.  Those  wards  should  be  promptly  evacuated 
to  wards  for  the  care  of  S.  hemolytic  "carriers"  on  the  one 
hand  and  for  "noncarriers"  on  the  other.  As  far  as  pos- 
sible patients  should  be  admitted  to  a  ward  until  it  is  filled 
and  then  another  ward  should  receive  consecutive  cases  in 
the  same  manner.  It  is  desirable  to  have  all  cases  in  each 
treatment  ward  in  the  same  stage  of  the  disease.  With 
this  system  of  ward  rotation  convalescent  wards  are  neces- 
sary, so  that  cases  requiring  a  period  of  hospitalization 
longer  than  the  average  may  bo  segregated,  thus  rendering 
treatment  wards  available  for  another  levy  of  acute  cases. 

3.  Strict  ward  technic  elaborated  to  prevent  transfer  of 
bacterial  infection  from  one  patient  to  another  must  be 
employed. 

4.  Throat  culture  for  identification  of  "carriers"  is  la- 
borious but  essential.  An  accurate  method  for  identifying 
and  reporting  "carriers"  as  speedily  as  possible  must  be 
eni] doyed.  A  competent  bacteriologist  is  essential.  A 
twenty-four  hour  interval  between  culture  and  its  report  is 
desirable.     The  following  scheme  is  recommended: 

(a)  A  culture  from  the  throat  made  on  admission  to  the 
observation  ward  (first  day  in  hospital). 

(h)  A  culture  made  on  the  first  day  in  the  treatment 
ward  (third  day  in  hospital). 

(c)  A  culture  made  one  week  later  (tenth  day  in  hos- 
pital). 

If  the  ward  incidence  of  hemolytic  streptocoooi  reaches 
10  per  cent,  especially  in  a  filled  ward,  the  cultures  should 
be  repeated  on  the  thirteenth  day  in  the  hospital.  If  the 
incidence  of  "carriers"  of  hemolytic  streptococci  increase 
rapidly,  cultures  on  alternate  days  should  be  made  so  that 
"carriers"   may  be  removed   from  the  ward.     AVherever 


SECONDARY  TNFUCTIOX    IX    WARD  TREATMENT  OF   MEASLES    321 

possible,  culturing  of  the  treatment  wards  as  units  should 
he  practiced. 

5.  Patients  developing  acute  symptoms  in  any  way  sug- 
gestive of  infection  with  S.  hemolyticus  should  be  imme- 
diately isolated ;  culture  from  the  throat  should  be  made  at 
once  and  final  disposal  of  the  patient  should  depend  apoii 
its  result. 

Carriers  of  Hemolytic  Streptococci 

During  the  winter  of  1917-18,  with  the  establishment  of 
the  army  camps,  it  very  soon  became  evident  that  in  many 
of  the  serious  and  fatal  complications  of  measles  and  other 
respiratory  diseases,  hemolytic  streptococci  were  playing 
a  very  important  role.  The  epidemic  prevalence  of  hemo- 
lytic streptococci  among  hospital  cases,  and  later  among 
men  on  duty  in  the  camps,  was  established  by  bacteriologic 
studies.  Prior  to  this  time  in  civil  life,  hemolytic  strep- 
tococci under  epidemic  conditions  had  been  studied  in  milk- 
borne  epidemics  of  sejjtic  sore  throat,  such  as  are  reported 
from  Chicago  in  1911-131 ;  from  Boston  in  19112 ;  and  from 
Baltimore  in  1911-123.  Contact  air-borne  infection  has  not 
been  emphasized  in  considering  the  dissemination  of  hemo- 
lytic streptococci.  Smillie4  reports  a  few  cases  of  hemo- 
lytic streptococcus  throat  infections  which  he  attributes 
to  contact  infection.  Conditions  within  the  arm}'  camps 
were  such  as  to  suggest  the  dissemination  of  hemolytic 
streptococci  by  contact  air-borne  infection.  Some  knowl- 
edge of  the  percentage  of  individuals  showing  positive 
throat  cultures  became  desirable  at  the  very  beginning  of 
studies  of  contact  dissemination  of  hemolytic  streptococci. 

Smillie  found  that  only  one  of  100  normal  throats  har- 
bored the  Beta  hemolytic  streptococci  of  Smith  and  Brown. 
Levy  and  Alexander5  report    the    presence    of    hemolytic 

iCapps,  J.  A.,  and  Davis,  D.  J.:  Arch.  Int.  Med.,  1914,  xiv,  650;  Illinois  Med.  Jour., 
November,   1912. 

2Windsor,   C.-E.  A.:     Jour.  Infect.   Dis.,   1912,  x.   73. 

3Hamburger,  D.   P.:      Tour.   Am.  Med.   Assn.,  April   13,   1912,   lviii,   1109. 

"Smillie,    W.    S.:     Jour.    Infect.    Dis.,    1917,  xx,   45. 

BDevy  and  Alexander:   Jour.  Am.   Med.   Assn.,    191S,   lxx,    1827. 


322      PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATOR'S   TRACT 

streptococci  in  83.2  per  cenl  of  healthy  men  al  Camp  Tay- 
lor, and  hemolytic  organisms  (not  definitely  identified  as 
streptococci)  in  14. S  per  cenl  of  recruits  arriving  at  Camp 
Taylor.  Irons  and  Marine6  Pound  hemolytic  streptococci 
among  70  per  cenl  of  healthy  men  at  Camp  Custer. 

Among  measles  patients  on  admission  to  the  hospital  at 
Port  Sam  Houston,  Colo  and  MacCallum7  report  11.4  per 
cent  and  CummingS,  Spruit  and  Lynch,"  35  per  cent  of 
throat  cultures  positive  for  hemolytic  streptococci.  At 
Camp  Taylor,  Levy  and  Alexander  report  77.1  per  cent 
positive  among  388  cases  of  measles  on  admission  to  the 
hospital. 

The  spread  of  hemolytic  streptococci  in  measles  wards 
was  shown  by  Cole  and  MacCallum  when  on  admission  11.4 
per  cent  of  eases  had  positive  throat  cultures,  38.6  per  cent 
after  Prom  three  to  five  days,  and  56.8  per  cent  after  from 
eight  to  sixteen  clays  in  the  ward.  Tn  our  study  of  hemo- 
lytic streptococci  with  measles  at  Camp  Funston,  2.6  per 
cent  of  the  cases  had  positive  throat  cultures  on  admission, 
12.8  per  cent  after  three  to  ten  days,  and  24.1  per  cent  after 
eight  to  twenty-three  days  in  the  hospital.  Tn  a  similar 
study  at  Camp  Pike  we  found  1.7  per  cent  positive  on  ad- 
mission; 10.!)  per  cent  after  one  week;  22.8  per  cent  after 
two  weeks;  26.2  per  cent  after  three  weeks;  and,  33.1  per 
cent  after  four  weeks  in  the  hospital. 

Hemolytic  Streptococci  in  the  Throats  of  Normal  Men.— 
The  percentage  of  normal  individuals  harboring  hemolytic 
streptococci  in  their  throats  was  investigated  in  three  dis- 
tinct classes  of  men,  classified  according  to  the  degree  of 
exposure  to  contact  infection. 

The  first  group  includes  men  largely  from  country  dis- 
tricts, cultured  within  an  hour  after  being  assembled  by 
their  local  draft  board.  The  laboratory  car  "Taster"  was 
sent  to  Hot  Springs,  Ark.  to  meet  the  November  draft  of 


'•Irons  and    Marine:     Jour.    Am.    Med.   Assn.,    1918,   lxx,   687. 
TCole   and    MacCallum:     Jour.    Am.    Med.    Assn.,    1918,    lxx.    1146. 
8Cummings,   Spruit   and  Lynch:     Jour.  Am.   Med.  Assn.,   1918,   lxx,   1066. 


SECONDARY   INFECTION"  IN  WAItl)  TREATMENT  OK  MEASLES    323 


men  to  l>c  sent  to  Camp  Pike.  These  men  were  returned 
to  their  homes  when  the  armistice  was  signed,  so  that  there 
was  no  opportunity  to  study  them  after  they  had  lived  un- 
der camp  conditions. 

The  second  gronp  includes  men  on  duly  in  Camps  Funs- 
ton  and  Pike.  These  men,  while  largely  from  country  dis- 
tricts, had  been  living  crowded  together  in  the  camp  for  a 
period  varying  from  a  few  weeks  to  several  months. 

The  third  group  includes  normal  men  resident  in  the 
base  hospitals  at  Ft.  Riley  and  Camp  Pike.  This  group 
includes  at  Camp  Pike  the  medical  personnel  of  the  measles 
and  measles  pneumonia  wards  and  represents  individuals 
most  exposed  to  contact  infection  with  hemolytic  strep- 
tococci. On  the  other  hand,  the  group  includes  doctors, 
nurses  and  seasoned  medical  detachment  men  who  are  per- 
haps less  susceptible  to  respiratory  infections  than  are  raw 
recruits. 

The  results  of  studies  of  these  groups  are  presented  in 
Tables  LXVI  and  LXVII. 

Table  LXVI 

Hemolytic  Streptococci  in  Throats  of  Normal  Men 
Not  Resident  in  the  Base  Hospital 


PLACE  OF  STUDY 

Ph 

r-l    M 

>  m 

£-<       ■ 

Eh    fe    § 

DATE 

o  S 

>Z    H    Eh 
H    t   m 

REMARKS 

^ 

Ph  W 

°  &  « 

-  in 

«  to  fi 

o  << 

2  o 

Hog 

£  o 

£  fe 

P-    Ph    X 

Camp  Funston, 

274 

60 

21.9 

Men    on   duty   in   camp    in- 

Kan., 

cluding  201  white  and  73 

Aug.,  1918. 

colored;     in     great     part 
newly    drafted    men 

Camp  Pike,  Ark., 

337 

25 

7.4 

Largely  white  men  on  duty 

Nov.  5  to  Dec.  10, 

in  camp 

1918 

Hot  Springs, 

*64 

0 

0.0 

Men  from  country  districts, 

Ark., 

assembled     by    the     local 

Nov.  12,  1918 

draft  board 

*  Sputum  or  saliva  cultures  on  50  of  these  men  yielded  1  positive  for  S. 
hemolyticus.  Sputum  or  saliva  injected  intraperitoneally  into  white  mice  and 
cultures  made  from  the  peritoneal  exudate  of  such  mice,  yielded  2  additional 
positives  in  the  same  group  of  50  men.  These  3  positive  cases  showed  very 
few  colonies  of  hemolytic  streptococci. 


324      PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATOR'S   TRACT 


Table  l.X\  II 

Strei    ococci  in  Throats  op  Normal  Men 
Resident  w  the  Base  Hospital 


PLACE  OF  STUD"! 
DATE 

o  w 

6, 

g    X 

E   y 

o  a 

-  - 
•  * 

O    o 

X     El. 

I'l  R   CENT 
POSITIVE  FOR 
EEM.    STREP. 

REMARKS 

Ft.   Riley,  Kan., 
Aug.,   L918 

24 

7 

29.2 

14   convalescent   patients  in 
a   Burgical   ward ;    10   lab- 
oratory workers 

Camp    Pike,   Ark.. 

Sept.  10  to 
Nov.  30,  1918. 

1.33 

22 

*7.5 

Personnel  of   measles  wards 

Per  cenl   positive,  mi  one   culture  only, 
erage  two  per  pei  son  as  follows : 

Cultured  No.  Cases 

Once  L53 

Twice  90 

3  times  39 

4  times  15 


Repeated  throat  cultures,  av- 

Positives 
11 


The  group  of  men  studied  at  Hot  Springs  represents 
individuals  among  whom  there  was  little  chance  for  contact 
dissemination  of  hemolytic  streptococci.  It  is  a  control 
series  of  men  from  outlying  districts  examined  before  their 
throat  bacteriology  has  been  complicated  by  the  inter- 
change  of  mouth  organisms  which  occurs  when  a  group  of 
men  are  crowded  into  close  quarters.  The  entire  absence 
of  hemolytic  streptococci  by  the  throat  culture  method  is 
noteworthy.  By  multiplying  the  chances  of  identifying 
hemolytic  streptococci  by  making  parallel  cultures  from 
the  saliva,  and  from  the  peritoneal  exudates  of  mice  in- 
oculated with  saliva,  hemolytic  streptococci  were  found, 
in  small  numbers,  in  '•]  instances.  The  findings  in  this 
group  were  only  three  throats  lightly  infected  with  hemo- 
lytic streptococci.  They  are  in  direct  contrast  with  the 
findings  among  individuals  living  in  camps  under  crowded 
conditions  and  arc  in  accord  with  the  findings  among  re- 
cruits arriving  in  cam])  as  recorded  by  Levy  and  Alexander. 

In  the  second  group,  men  living  for  a  time  in  camp,  the 
findings  at  Camp  Funston  and  at  Camp  Pike  show  rather 


SECONDARY  INFECTION  IN   WARD  TREATMENT  OF  MEASLES    325 

striking  differences.  The  lower  percentage  incidence  at 
Camp  Pike  is  the  more  remarkable  since  the  studies  were 
made  soon  after  the  influenza  epidemic  had  swept  the  camp 
and  made  necessary  the  hospitalization  of  about  20  to  25 
per  cent  of  the  camp  population. 

In  the  third  group,  namely,  individuals  resident  in  the 
hospital,  percentage  rates  at  Camp  Funston  are  slightly 
higher  than  for  men  resident  in  camp.  This  difference 
disappears  for  the  entire  group  at  Camp  Pike  if  we  con- 
sider a  single  throat  culture,  as  we  must  for  the  sake  of 
comparison.  The  majority  of  these  individuals  at  Camp 
Pike  served  in  measles  wards  from  which  patients  carry- 
ing hemolytic  streptococci  were  removed  at  weekly  inter- 
vals. Seven  and  one-half  per  cent  of  the  ward  personnel 
were  positives  when  first  cultured.  An  additional  7.5  per 
cent  acquired  the  streptococcus  while  under  observation. 

Duration  of  the  "Carrier"  State. — Unfortunately  there 
are  very  few  observations  with  regard  to  the  duration  of 
the  "carrier"  state  which  can  be  determined  only  by  re- 
peated cultures  at  short  intervals.  \Ve  have  made  no  ob- 
servations of  the  duration  of  the  "carrier"  state  in  healthy 
men.  Two  hundred  and  forty-two  individuals  carrying 
hemolytic  streptococci  were  identified  in  the  ward  treat- 
ment of  measles.  All  except  37  of  these  cases  were  "non- 
carriers"  when  first  observed.  The  remaining  205  include 
166  contact  "carriers"  and  39  patients  with  acute  symp- 
toms of  infection  by  hemolytic  streptococci. 

The  complete  record  of  throat  cultures  on  these  cases  is 
presented  in  Table  LXVIII. 

Group  I  includes  37  cases  positive  for  hemolytic  strep- 
tococci on  admission. 

(a)  Twenty-two  of  these  remained  positive  throughout 
the  period  of  observation.  Four  patients  became  negative 
after  one  or  two  weeks  and  later  showed  positive  findings, 
leaving  the  hospital  as  positives.  These  are  classified  as 
"irregular."    The  results  of  culture  were  as  follows:  Cul- 


326      PNEUMONIAS  AXii   [NFECTIONS  OF   RESP]  RATOR"5    TRACT 


Table   LXVIII 

Results  of  Throat  Cultures  ix  242  Hospital  Patients  Identified  as 

"Carriers""  o)-  Eemolytic  Streptococci;  Cultures  Taken  at 

Weekly    [nterv \i.s 


p 

- 

a 

- 
- 

u 

-J 
'- 

- 

3 
— 

3 

'_ 

•o 
c 

- 
- 

3 

o 

■3 
- 

CO 

; 

3 
3 

■- 

1 

3 

3 
- 

- 
IO 

3 
- 

- 
•- 

- 

- 
t- 

- 
— 

- 

- 
- 
= 

3 
- 

— . 

- 
3 

3 
- 

9 

- 

3 

3 

•_ 

X, 

02 

- 

°  n 
u  5 

-9 

o  - 
o  o 

£2 

E  g 

D  = 
O    ft 

"■  -= 

Is 

1 

1 

i| 

.". ,   Cases 

1      1 

+  1       1       1 

1      1           7 

+  1  +  1       1 

1     1     7 

+1+1+1 

6 

+1+1+1+ 

2 

+  1-1       1 

8 

+1-1-1 

1 

+1-1-1- 

- 

1 

+1+1-1 

1 

+1-1+1 

12 

+  1-1-1- 

- 

+ 

+ 

+ 

1 

+1+1-1- 

+ 

+ 

+ 

1 

ii| 

J7|Cases 

-l  +  l     1 

26 

3 

-l+l+l 

12 

5 

-1+1+1+ 

2 

2 

-l+l-l 

9 

1 

-|+j-j- 

0 

1   | 

-l+l+l- 

2 

1 

-1+1+1+ 

+ 

- 

- 

+ 

- 

1 

-1+1-1+ 

2 

in 

74|Cases| 

I 

-1-1+1 

38 

5 

^r 
^r 

-l  +  l  + 

5 

3 

-1+1+ 

+ 

4 

1 

-1-1+1+ 

+ 

+ 

0 

2 

-i-i+i- 

- 

- 

0 

1   | 

-i-i+i-i 

4  I 

-1-1+1  + 

- 

- 

- 

- 

1  ! 

-1-1+1+ 

- 

0 

2 

-1-1+1+ 

- 

- 

- 

1 

-1-1+1+ 

+ 

+ 

- 

0 

1 

-i-i+i- 

+ 

1 

-i-i+i- 

+ 

+ 

2 

-i-i+i- 

+ 

+ 

+ 

1 

-i-i+i- 

- 

+ 

+ 

1 

-1-1+1+ 

+ 

- 

- 

+ 

1 

i 

1 

SECONDARY  INFECTION  IN  WARD  TREATMENT  OE   MEASLES    327 
Table  LXVIII— Cont'j> 


CM 

b 
o 

3 

3 
u 

+J 
w 

rH 

u 
3 

3 

o 
c 

3 

3 
o 

CO 

9 

3 

3 
o 

.3 

■~ 

3 

3 
o 

A 

3 
o 

A 

CO 

3 

6 

A 
t- 

9 

6 
A 

00 

3 
3 

o 

A 

3 
u 

o 

4) 

3 
M 

3 
u 

A 
-t-> 

— 

u 

3 

3 
o 

A 
+-> 

CM 

w 

fll 

o  r 
O  S 

o  : 

o  o 

-  /. 

-  3 

ffi.2 

cu  a! 
3S 

°  a 
<!  g 

rj    3 

So 

o  s- 

1 

IV 

34  Cases 

1 

|                  | 

-|-|-!+ 

1 

1      l^ 

4 

-  |  -  |  - 

4- 

+ 

I         5 

-  |  -  |  - 

1 

+ 

+ 

4 

-  |  -  |  - 

4- 

- 

1     3 

1 

-  |  -  |  - 

4- 

- 

- 

! 

1     1 

-  |  -  |  - 

4- 

+ 

- 

|     1 

_  |  _  |  _ 

+ 

+ 

+ 

- 

!    l 

_  |  _  |  _ 

4- 

- 

- 

+ 

4- 

I    l 

-  |  -  |  - 

4- 

+ 

- 

- 

- 

- 

- 

0 

1 

V 

16  Cases 

-  |  -  |  - 

- 

4- 

1    1 

1 

_  |  _  |  _ 

- 

+ 

+ 

1 

1 

_  |  _  |  _ 

- 

+ 

- 

1    3 

1 

-  |  -  |  - 

- 

4- 

- 

- 

- 

1    o 

-2, 

1    1 

-  |  -  |  - 

- 

+ 

+ 

- 

1    1 

-  |  -  I  - 

- 

4- 

- 

+ 

2 

-  |  -  |  - 

- 

+ 

+ 

- 

4- 

|     1 

-  I  -  1  - 

- 

+ 

+ 

- 

- 

- 

+ 

|     1 

VI 

7  Cases 

-  |  -  |- 

+ 

|     1 

-  |  -  |  - 

+ 

+ 

1      2 

-  |—  |  - 

+ 

- 

3 

_  |_  |  _■ 

- 

- 

+ 

- 

- 

!     1 

VII 

4  Cases 

-|  -|- 

4- 

""1     2 

-  |  -  |  - 

- 

- 

- 

4- 

4- 

|     1 

|     1 

VIII 

3  Cases 

|  -  |  -  |  - 

- 

- 

- 

- 

4- 

!     2 

1  -  1  _  1  _ 

4- 

+ 

+ 

1 

|      | 

MM 

MM 

MM 

1 

1 

| 

1 

1 

328      PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATORY  TRACT 

in  it  J  once  only,  7  :  positive  after  one  week,  7:  positive  after 
two  weeks,  6;  positive  after  three  weeks,  2;  irregular,  4. 

(fe)  Eleven  of  the  patients  entering  as  positives  became 
negative,  K'  after  one  week  and  1  after  two  weeks. 

This  group  of  eases  furnishes  no  data  concerning  the 
duration  of  the  "carrier"  slate,  since  all  eases  were  posi- 
tive when  first  observed.  Tn  30  per  cent  of  instances  hemo- 
lytic streptococci  disappeared  within  the  firsl  two  weeks 
of  observation. 

Groups  II  to  VIII  include  205  patients  who  became  pos- 
itive at  some  time  during  their  stay  in  the  hospital..  The 
arrangement  in  groups  depends  upon  the  length  of  time 
the  patients  remained  in  the  hospital  before  acquiring  S. 
hemoh  liens.  Ninety-five  of  these  patients  had  no  further 
cultures  after  the  initial  positive  culture.  Fourteen  appear 
as  "irregular,"  as  defined  above.  These  two  classes  of 
cases  are  omitted  in  the  following  summary  of  these  groups. 
The  initial  positive  culture  is  arbitrarily  considered  the 
day  of  infection  and  subsequent  cultures  mark  off  weekly 
intervals. 

(a)  Thirty-nine  patients  had  acute  infections  due  to 
hemolytic  streptococci.  Thirteen  of  these  patients  passed 
from  observation  after  their  initial  positive  culture.  The 
eases  with  repeated  cultures  after  initial  positive  may  he 
summarized  as  in  Table  LXIX. 


Table  LXIX 


NO.    PATIENTS 
CULTURED 

NO.     BECOMING 
NEGATIVE 

I'll;     CENT 
BECOMING 
NEGATIVE 

Reeultured  after  one  week 
Recull  iii-'il  ,-i  fter  two  weeks 
Reeultured  after  three  weeks 
Reeultured  after  four  weeks 

26 
14 

7 
2 

7 
8 
4 
2 

26.9 
57.1 
57.1 

100.0 

The  records  within  this  small  group  of  cases  indicate 
that  hemolytic  streptococci  tend  to  disappear  with  the  pass- 
ing of  t he  acute  infection. 


SECONDARY  INFECTION   IN  WARD  TREATMENT  OE   MEASLES    329 

(b)  One  hundred  and  sixty-six  contact  "carriers"  are 
included  in  Groups  II  to  VIII.  Eighty-two  of  these  passed 
from  observation  after  their  initial  positive  culture  and 
14  appear  as  "irregular."  The  cases  will)  repeated  throat 
cultures  after  the  initial  positive  are  summarized  in  Table 
LXX. 

Table  LXX 


NO.    PATIENTS 

NO.     BECOMING 

PES    CENT 
BECOM  1  •  <; 
NEGATIVE 

CULTURED 

NEGATIVE 

Recultured  after  one  week 

70 

26 

37.1 

Recultured  after  two  weeks 

22 

9 

40.9 

Recultured  after  three  weeks 

5 

5 

100.0 

Recultured  after  four  weeks 

4 

4 

100.0 

These  records  indicate  that  contact  carriers  in  great  part 
harbor  hemolytic  streptococci  during  short  intervals.  A 
longer  period  of  observation  after  the  disappearance  of 
hemolytic  streptococci  would  have  been  desirable  in  many 
instances.  Some  patients  were  followed  with  consistently 
negative  cultures  during  three,  four  and  five  weeks  after 
hemolytic  streptococci  had  disappeared. 

It  is  difficult  to  explain  those  instances  in  which  nega- 
tive cultures  are  interposed  between  positives.  Where  one 
negative  interrupts  positive  cultures,  it  is  possible  that  the 
throat  culture  failed  to  demonstrate  hemolytic  streptococci 
which  were  present.  Such  cases  in  this  series  fall  within 
the  limits  of  the  percentage  error  of  throat  culture  iden- 
tification. Where  two  or  three,  or  even  four  negative  cul- 
tures intervene,  reinfection  is  not  impossible. 

Relation  of  S.  Hemolyticus  ''Carriers"  to  the  Compli- 
cations of  Acute  Respiratory  Diseases. — In  the  present 
study  of  measles  it  has  been  shown  that  pneumonia  fol- 
lowing measles  has  been  no  more  common  in  "carriers" 
than  in  "noncarriers."  Nevertheless,  pneumonia  occur- 
ring in  badly  infected  wards  has  been  modified  by  strep- 
tococcus complications. 

More  cases  of  otitis  media  have  appeared  in  "carriers" 
than  in  "noncarriers."     The  possibility  that  mild  otitis 


330      PNEUMONIAS  AND   [NFECTIONS  03?   RESPIRATOR?  TRACT 

media,  which  would  ordinarily  pass  unnoticed,  might  be- 
come  evident  as  the  result  of  streptococcus  invasion  must 
lie  considered.  Levy  and  Alexander  have  made  an  impor- 
tant contribution  to  our  knowledge  of  the  role  of  hemolytic 
streptococci  in  measles.  They  find  thai  "carriers"1  of 
hemolytic  streptococci  among  measles  patients  are  espe- 
cially   predisposed   to  complications   following  measles. 

Their  cases  were  drawn  from  a  camp  population  highly 
saturated  with  S.  hemolyticus  "carriers."  In  the  organ- 
ization from  which  89  per  cent  of  their  patients  with 
measles  came,  there  were  83  per  cenl  hemolyticus  ''car- 
riers" among  men  on  duty.  Among  patients  with  measles. 
throat  cultures  were  positive  for  hemolytic  streptococci  on 
admission  in  77  per  cent.  It  is  evident  that  all  patients 
with  measles  have  been  exposed  to  hemolytic  streptococci 
during  the  first  day  or  two  after  admission.  Failure  to 
carry  streptococcus  would  appear  to  be  dependent  upon 
ability  to  resist  it  rather  than  upon  lack  of  opportunity  for 
acquiring  it.  Of  388  cases  observed  by  Levy  and  Alexander 
only  7!)  were  "noncarriers"  of  hemolytic  streptococci  on 
admission,  and  of  these,  27  became  positive  while  under 
observation  :  only  52  remain  as  "noncarriers"  of  hemolytic 
streptococci.  This  small  group  must  be  regarded  as  a 
highly  selected  one,  composed  of  individuals  more  than  or- 
dinarily resistant  to  hemolytic  streptococci  and  perhaps  to 
all  complications  of  measles.  The  chances  are  that  these 
52  cases  placed  under  any  circumstances  might  very  well 
have  been  among  the  large  number  of  measles  cases  in 
which  no  complications  develop. 

furthermore,  it  is  not  unlikely  that  any  complication  of 
measles  may  be  modified  by  a  streptococcus  secondarily 
when  about  85  per  cent  of  the  cases  show  S.  hemolyticus  in 
the  throat.  The  complications  in  the  cases  of  Alexander 
and  Levy  appear  to  have  been  caused  in  large  part  by 
streptococcus,  but  a  complete  bacteriologic  study  of  them  is 
not   recorded.     Complications  among  streptococcus  "car- 


SECONDARY  INFECTION  JN   WARD  TREATMENT  OE   MEASLES    33] 

riers"  are  not  identical  with  complications  due  to  the 
streptococcus,  and  it  is  desirable  to  know  vvhal  percentage 
of  complications  actually  due  to  hemolytic  streptococci  oc- 
curred among  the  85  per  cent  of  patients  with  measles  who 
carried  hemolytic  streptococci. 

Summary. — No  hemolytic  streptococcus  complications 
occurred  in  112  cases  of  measles  observed  at  Ft.  Riley, 
among  which  streptococcus  "carriers"  rose  from  2.6  per 
cent  on  admission  to  24.1  per  cent  before  discharge  from 
the  hospital.  The  percentage  of  " carriers"  of  hemolytic 
streptococci  among  normal  men  in  the  camp  supplying  these 
cases  was  about  25.5  per  cent. 

The  influenza  epidemic  and  a  small  epidemic  of  measles 
occurred  in  part  simultaneously  at  Camp  Pike  during  Sep- 
tember and  October,  1918.  The  complications  following- 
measles  at  Camp  Pike  were  to  a  considerable  extent  de- 
pendent upon  the  combined  effects  of  influenza  and  measles. 

Thirty-five  per  cent  of  the  measles  patients  showed  throat 
cultures  positive  for  B.  influenza?  on  admission  to  the 
hospital.  On  repeated  cultures,  this  rose  to  84  per  cent  be- 
fore discharge. 

Ward  separation  of  cases  of  measles  carrying  hemolytic 
streptococci  in  their  throats  and  cases  not  carrying  these 
organisms  were  practiced  in  handling  this  epidemic.  Of 
867  cases  of  measles  treated  in  this  manner,  37  were  posi- 
tive for  hemolytic  streptococci  on  admission,  and  205  de- 
veloped positive  throat  cultures  for  these  organisms  dur- 
ing their  period  of  observation  in  the  hospital. 

At  Camp  Pike,  the  percentage  incidence  of  S.  hemolyti- 
cus  "carriers,"  on  admission  to  the  measles  wards,  was 
4.2  per  cent.  In  cases  recultured  offer  one  week,  it  was 
10.9  per  cent;  after  two  weeks  22.8  per  cent;  after  three 
weeks  26.2  per  cent;  and  after  four  weeks  33.1  per  cent. 
The  weekly  development  of  "carriers"  in  the  "clean" 
treatment  wards  was  during  the  first  week  9.1  per  cent; 
during  the  second  week  17.4  per  cent ;  during  the  third 


332      PNEUMONIAS  AND   INFECTIONS  OF   RESPIRATOR'S  TRACT 

week  17. -I  per  cent;  and  during  the  fourth  week  17.4  per 
cent. 

The  principal  complications  of  these  867  cases  of  measles 
at  Camp  Tike  were:  pneumonia,  56  cases;  otitis  media,  48 
eases,  with  subsequent  mastoiditis  in  23  eases,  2  of  which 
had  extensions  to  the  meninges  and  brain.  The  greater 
part  of  the  pneumonia  occurred  early  in  the  period  of  ob- 
servation, while  most  of  the  otitis  media  occurred  later. 
Incidence  of  hemolytic  streptococci  was  low  during  the 
pneumonia  period  and  high  during  the  prevalence  of  otitis 
media. 

Hemolytic  streptococci  complicated  9  of  these  pneumo- 
nias; caused  a  large  percentage  of  otitis  (bacteriology  in- 
complete), and  21  of  the  23  eases  of  mastoiditis. 

The  bacteriology  of  35  of  the  56  pneumonias  showed: 
Pneumococcus  Type  II  atypical,  in  36  per  cent,  Type  IV  in 
22.9  per  cent,  Type  I  in  2.8  per  cent  and  Type  III  in  2.8  per 
cent;  hemolytic  streptococci  in  22.4  per  cent;  and  B.  influ- 
enza1 in  88.6  per  cent. 

The  culturing  of  wards  as  units  revealed  widespread  con- 
tact dissemination  of  hemolytic  streptococci,  at  times  25 
to  50  per  cent  of  the  patients  in  a  ward  becoming  "car- 
riers" within  the  period  of  a  week.  Streptococcus  pneu- 
monias, otitis  media  and  its  complications  were  furnished 
in  large  part  by  wards  in  which  active  dissemination 
occurred. 

Streptococcus  complications  did  not  occur  among  37  pa- 
tients who  were  "carriers"  of  hemolytic  streptococci  when 
admitted  to  the  hospital. 

The  epidemic  dissemination  of  hemolytic  streptococci  oc- 
curs in  measles  wards,  and  is  a  serious  danger.  Many  pa- 
tients whose  throats  become  infected,  develop  no  symptoms. 
In  some  instances  streptococcus  invades,  and  renders  much 
more  serious  lesions  caused  by  other  microorganisms. 

Methods  to  prevent  transfer  of  infection  within  the  ward 
and  separation  of  "carriers"  from  "noncarriers"  in  dif ■ 


ferent  wards  are  efficient  in  keeping  epidemic  dissemina- 
tion of  hemolytic  streptococci  under  control.  Frequent 
throat  cultures  and  prompt  report  of  the  results  of  cul- 
tures are  essential. 

The  dissemination  of  B.  influenzas  in  patients  with  meas- 
les was  not  controlled  by  segregation  of  "carriers"  and 
"noncarriers"  of  this  organism  as  identified  by  throat  cul- 
tures in  separate  wards. 


CHAPTEE  VI 

THE  PATHOLOGY  AND  BACTERIOLOGY  OF 
PNEUMONIA    FOLLOWING   MEASLES 

Eugene  L.  Opie,  M.I). ;  Francis  (i.  Blake,  M.D.;  James  C. 
S.mm.i..  M.I).;  AND  Thomas  M.  Rivers,  M.D. 

Atiion^'  L8  autopsies  upon  men  who  have  died  with  pneu- 
monia following  measles  there  are  pulmonary  lesions  rep- 
resenting almost  every  type  of  pneumonia  which  has  been 
found    in    association  with  influenza.     In  most    instances 

pneumonia  made  its  appearance  during  the  second  week  of 
measles  and  death  occurred  during  the  third  week.  Of  16 
instances  in  which  the  record  is  definite,  pneumonia  had  its 
onset  during  the  first  week  of  measles  in  4  instances,  during 
the  second  week  in  11  instances,  and  in  one  instance  (Au- 
topsy 390)  perhaps  not  referable  to  measles  in  the  fifth 
week.  The  duration  of  pneumonia  varied  from  three  to 
thirty-two  days;  in  10  instances  it  did  not  exceed  one  week, 
in  5  instances  it  was  between  one  and  two  weeks  and  in  one 
instance,  thirty-two  days.  When  the  duration  of  pneu- 
monia exceeded  ten  days  some  evidence  of  chronic  pul- 
monary disease  was  found  at  autopsy. 

The  same  lack'  of  correspondence  between  clinical  diag- 
nosis and  pulmonary  lesions  noted  with  influenza  was  found 
following  measles.  Jn  accordance  with  the  prevailing 
opinion  concerning  the  character  of  pneumonia  following 
measles,  the  diagnosis  of  bronchopneumonia  was  made  in 
13  instances  and  in  all  of  these  cases  bronchopneumonia  was 
found  at  autopsy.  The  diagnosis  of  lobar  pneumonia  was 
made  5  times  and  was  correel  only  once.  Nevertheless, 
lobar  pneumonia  was  present  4  times,  but  was  recognized 
only  once  (  Autopsy  4S(i.)     Failure  to  recognize  lobar  pneu- 

334 


PATHOLOGY  AND  BACTERIOLOGY    FOLLOWING   MEASLES 


Cn  Cn  Cn  4-       4-4-       4-4-4-4-4-4-4-4-4-4-       4-  Cm 
O  O  O  O        OO        CO  CO  CO  Cn  Cn  4-  4-  4-  4-  Cm        Cm  O 
CO  ^1  Cn  Ov        1^  *-        04-*-Cm04-Cm1w>—  -G        COO 

NO.  OF  AUTOPSY 

nno^    ^^    n^^^ ^ss^?;^^    <j:2 

RACE 

.,.      ^             **  ^  s            4-  Cn  Cm  1-m       t^i            i— 

b1  H'  ±-  :f    *  J?    om^4-oo^--^-^-o    <^  ~ 
ss  33     n.3     aaaaas  as  3  a     3  s 

LENGTH  OE   MILITARY 

SERVICE 

t—H-^4^            K»  •—            H-tNi4-—h-            WH^H           Ki  Cm 

OS  4-*  ON  CM       OvO        MO  _|_  Cm  >0  sO  Cm  ^i  On  4-        1m.  Cn 

DURATION  OF  ILLNESS 

Cm        p—                                               MMl-K       » 
Cn  CM  Ov  N3        h- Cn        CO  -J  Cm  O  Cn  Cm  4-    1     ^-  •—        I 

oO\ 

DURATION  OE  PNEUMONIA 

wcawr    rw    rrararawrawrtaw    car 

CLINICAL  DIAGNOSIS 

lT)h0       Tl 

^d  *"0  '"d  ^o  *  '■o  *"0  *"0  ^o  "tj    ""U 

PURULENT  BRONCHITIS 

+  : 

+:     : 

+:::+:::::     : 

LOBAR  PNEUMONIA 

g; 

+     g 

+++gg-f-g+g    +  S 

PERIBRONCHIOLAR 
CONSOLIDATION 

:     ++   : 

+  _ 

:  ++    :  : 

HEMORRHAGIC  PERI- 
BRONCHIOLAR CONSOL. 

+  + 

+++. 

+ 

+++   ++ 

LOBULAR  CONSOLIDATION 

g 

g 

§ 

g; 

:  g:  g 

PERIBRONCHIAL 
CONSOLIDATION 

2 

+ 

Z 

+ 

ABSCESS 

+ 

+ 

+ 

INTERSTITIAL  SUPPURA- 
TIVE PNEUMONIA 

MULTIPLE  ABSCESSES   IN 
CLUSTERS 

M 

KM 

w 

M 

EMPYEMA 

+  - 

r 

+++ 

:  + 

++    : 

BRONCHIECTASIS 

+  - 

f 

++ 

:  + 

:  :      + 

UNRESOLVED  BRONCHO 
PNEUMONIA 

+   : 

:  +  ; 

ORGANIZING  BRONCHITIS 

— 

re 

3 

re 

3 

2« 

3  " 

—  -. 

3S 

CO 
re 

3 

J) 

re 

3 
3d 

co 

3 

22 

3  3 

-"a 
3 

1 5 
3  > 

3 
f) 

re 
3 

race 
Z: 

o  . 

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re  . 

2! 

3 

CO 

3* 
re 

3 

'A' 

3  . 

d  ; 

3 

CO 

3" 
ti 

3 

~ 

/ 

o 

CO 

3" 
ti 

3 

BACTERIA  IN  SPUTUM 

re 

3 

P 
M 

5' 
V 

re 

3 

CO 

- 

re 
3 

=  ' 

CO 

P 
= 

5 

= 
2 

P 
CO 

— 
n 

5 

ra 

w 

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n  P 

;  a 
— — 

a 

- 
CO 

-- 

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BACTERIA    IN    BLOOD    OF 
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336      PNEUMONIAS  AND   INFECTIONS  03?   RESPIRATOR'S    TRACT 

monia,  was  doubtless  due  in  pari  at  least  to  its  association 
with  purulent  bronchitis  and  peribronchiolar  pneumonia 
(Table  LXXI). 

Changes  in  Bronchi.-  The  changes  in  the  bronchi  do  not 
differ  in  character  Prom  those  associated  with  pneumonia 
following  influenza.  Purulenl  bronchitis  recognized  at  au- 
topsy by  the  presence  of  mucopurulent  material  in  the 
small  bronchi  was  found  in  a  much  Larger  proportion  of 
Instances  in  this  group  of  autopsies  occurring  in  13  of  18 
instance-  (72.2  per  cent),  whereas  it  was  present  in  only 
55.6  per  cent  of  autopsies  on  individuals  with  pneumonia 
following  influenza.  There  was  peribronchial  hemorrhage 
recognizable  on  gross  examination  in  3  autopsies  and  mi- 
croscopically in  3  additional  instances. 

Bronchiectasis  was  present  in  a  considerable  proportion 
of  these  autopsies,  dilatation  of  bronchi  being  noted  in  7, 
but  it  was  usually  moderately  advanced  and  at  times  limited 
to  the  bases  of  the  lungs.  The  short  duration  of  respira- 
tory disease  perhaps  explains  the  infrequency  of  advanced 
bronchiectasis.  The  incidence  of  the  lesion  is  greater  with 
measles  (43.7  per  cent)  than  with  influenza  (22.4  per  cent). 

Microscopic  changes  in  the  bronchi  do  not  differ  from 
those  found  after  influenza.  Evidence  of  acute  inflamma- 
tion, often  hemorrhagic  in  character,  is  found  within  the 
lumen  of  the  bronchus  and  in  the  tissues  immediately  in 
contact  with  the  lumen.  Not  infrequently  the  epithelium 
is  lost ;  there  is  superficial  necrosis  and  deposition  of  fibrin 
upon  the  surface  and  within  the  tissue.  In  the  deeper  tis- 
sues of  the  bronchial  wall  there  is  infiltration  with  lymphoid 
and  plasma  cells,  which  in  the  larger  bronchi  is  particularly 
advanced  about  the  mucous  glands  of  which  the  acini  ex- 
hibit degenerative  changes.  With  the  onset  of  chronic 
changes  new  formation  of  fibrous  tissue  occurs  in  the  wall 
of  the  bronchus  and  in  the  contiguous  interalveolar  walls. 
The  lining  epithelium  often  loses  its  columnar  cells  and 
assumes  a  squamous  type. 


PATHOLOGY  AND  BACTERIOLOGY   FOLLOWING  MEASLES       361 

Changes  in  the  bronchi  with  bronchiectasis  have  been 
similar  to  those  following  influenza.  Weakening  of  the 
wall  permitting  dilatation  is  brought  about  by  necrosis  ex- 
tending outward  Prom  the  lumen  a  varying  distance  into 
the  bronchial  wall  and  permitting  the  formation  tears  which 
diminish  resistance  to  intrabronchial  pressure. 

Lobar  Pneumonia. — Lobar  pneumonia  following  measles 
occurred  in  4  instances.  Onset  in  these  cases  was  on  ap- 
proximately the  9th,  10th,  11th  or  14th  day  of  measles;  the 
onset  of  bronchopneumonia  bore  a  similar  time  relation  to 
the  onset  of  measles,  the  average  interval  being  nine  days. 
Hepatization  with  lobar  pneumonia  was  in  1  instance  red,  in 
3  instances  gray,  and  in  all  save  1  instance  the  consolidation 
was  firm  and  coarsely  granular  on  section.  In  the  excep- 
tional instance  the  greater  part  of  the  right  upper  lobe  was 
laxly  consolidated  and  rather  finely  granular  but  the  mi- 
croscopic appearance  was  in  all  instances  that  of  lobar 
pneumonia.  Lobar  pneumonia  in  2  of  these  cases  was  as- 
sociated with  purulent  bronchitis  present  in  parts  of  the 
lung  that  had  not  undergone  consolidation,  whereas  in  the 
other  2  instances  there  were  acute  bronchitis  and  peri- 
bronchiolar pneumonia  recognized  by  microscopic  exam- 
ination. 

In  one  instance  hepatization  of  the  lung  presented  some 
noteworthy  features. 

Autopsy  450. — G.  D.,  white,  aged  twenty-one,  a  farmer,  resident  of  Arkan- 
sas, had  been  in  military  service  twenty-nine  days.  Onset  of  illness  began 
on  October  2,  nineteen  days  before  death,  and  on  admission  on  the  same  day 
the  diagnosis  of  measles  was  made.  Signs  of  pneumonia,  regarded  as  bron- 
chopneumonia, were  recognized  five  days  before  death.  Three  days  later 
there  was  otitis  media  and  paracentesis  was  performed.  On  October  3  and  10 
neither  S.  hemolyticus  nor  B.  influenzae  was  found  in  the  sputum;  on  Octo- 
ber 17  and  20  S.  hemolyticus  was  not  found  but  B.  influenzae  was  present. 

Anatomic  Diagnosis. — Acute  lobar  pneumonia  with  gray  and  red  hepati- 
zation in  right  upper  and  lower  lobes;  edema  and  peribronchial  hemor- 
rhage in  left  lung. 

The  entire  lower  lobe  of  the  right  lung  (Fig  29)  with  the  exception  of 
a  narrow  air-containing  zone  in  contact  with  basal  surface  is  firmly  con- 
solidated.    The  greater  part   of  the   consolidated   tissue   is  yellowish   gray. 


338      PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATORY   TRACT 


Fig  29  -Lobar  pneumonia  following  measles,  showing  extension  of  gray  hepatiza- 
tion from  lower  to  upper  lobe  through  a  tlcfecl  in  the  septum  separating  the  two  lobes. 
Autops 


PATHOLOGY  AND  BACTERIOLOGY  FOLLOWING  MEASLES      339 

firm  and  coarsely  granular.  The  uppermost  pari  of  the  consolidated  tissue 
is  softer  than  elsewhere  as  if  it  has  undergone  autolysis.  The  lowermost 
part  of  the  consolidated  tissue  in  a  zone  from  2.5  to  .'5.5  em.  in  breadth  is 
firmly  consolidated  but  deep  red.  The  bronchi  contain  stiff  plugs  of  fibrin. 
In  the  upper  lobe  continuous  with  the  consolidated  part  of  the  lower  is  a 
semicircular  patch  of  yellowish  gray  consolidation.  It  overlies  the  line  of 
the  interlobular  cleft  at  the  site  of  a  break  in  its  continuity.  Consolidation 
appears  to  have  spread  from  the  lower  lobe  into  the  upper  at  the  site  where 
the  alveolar  tissue  of  the  two  lobes  is  continuous  but  is  absent  from  that 
part  of  the  upper  lobe  separated  from  the  lower  by  the  interlobular  cleft. 
This  semicircular  patch  of  yellowish  gray  consolidation  is  separated  from 
air  containing  tissue  of  the  upper  lobe  by  a  zone  of  red  hepatization  about 
1  cm.  in  thickness. 

Bacteriologic  examination  showed  the  presence  of  Pneumococcus  IV  in 
the  blood  of  the  heart;  B.  influenzas  alone  was  obtained  from  the  right 
lower  lobe  and  B.  influenzas  and  staphylococcus  from  the  left  main  bron- 
chus. 

The  distribution  of  lobar  pneumonia  in  the  foregoing 
autopsy  indicates  that  it  has  spread  like  a  wave  from  the 
upper  part  of  the  lower  lobe  (Fig.  32)  penetrating  into  the 
upper  where  the  alveolar  tissue  of  the  two  lobes  is  in  con- 
tact; gray  hepatization  is  everywhere  separated  from  air 
containing  tissue  by  an  advancing  zone  of  red  hepatiza- 
tion. 

It  may  be  assumed  that  lobar  pneumonia  was  caused  by 
Pneumococcus  II  atypical  in  3  instances  although  it  was 
recovered  from  the  lungs  only  twice,  for  in  the  third  in- 
stance (Autopsy  486)  it  was  found  in  the  bronchus  and  in 
the  inflamed  pleural  cavity;  pneumococci  were  doubtless 
previously  present  in  the  lung,  but  had  disappeared  at  least 
from  that  part  from  which  the  culture  was  made.  Pneu- 
mococcus IV  was  evidently  the  cause  of  pneumonia  in  1 
instance  (Autopsy  450),  for  it  was  found  in  the  blood  of 
the  heart  although  it  was  absent  in  the  culture  from  the 
lung. 

Little  significance  can  be  attributed  to  the  observation 
that  B.  influenza?  was  present  in  pure  culture  in  the  lungs 
from  Autopsies  450  and  486,  for  the  presence  of  Pneumo- 
cocci IV  in  the  blood  of  the  heart  in  Autopsy  450  and  of 


.'HO      PNE1  MONIAS  A\H   [NFECTIONS  OF   RESPIRATOR'S   TRACT 

Pneumococcus  1 1  atypical  in  the  pleura  in  Autopsy  486  fur- 
nishes evidence  in  view  of  the  occurrence  of  lobar  pneu- 
monia thai  pneumococci  had  disappeared  Prom  the  Lungs. 
B.  influenzae  was  found  both  in  the  lungs  and  bronchus  or 
iu  the  bronchus  alone  in  3  of  these  4  cases. 

The  relation  of  hemolytic  streptococci  to  the  lesion  is  of 
interest.  In  3  of  4  instances  of  lobar  pneumonia  this  mi- 
croorganism had  entered  the  bronchi  but  was  not  round  in 
tlic  bums  or  in  the  heart's  blood;  and  gross  and  histologic 
examination  showed  none  of  the  lesions  which  are  usually 
caused  by  it.  In  1  instance  (Autopsy  508)  hemolytic  strep- 
tococci, absent  from  the  throat  when  the  patient  was  ad- 
mitted to  the  hospital  with  measles  sixteen  days  before 
death,  appeared  in  a  culture  made  five  days  later  and  was 
subsequently  found  three  times;  it  had  penetrated  into 
the  bronchus  but  failed  to  roach  the  lung.  Observations 
made  upon  lobar  pneumonia  following  influenza  have  shown 
the  relative  insusceptibility  of  lobar  pneumonia  with  gray 
hepatization  to  secondary  infection  with  hemolytic  strepto- 
cocci (p. Kid).  Autopsy  508  demonstrates  thai  occurrence  of 
hemolytic  streptococci  in  the  sputum  of  a  patient  with  pneu- 
monia does  not  furnish  conclusive  proof  of  the  existence  of 
si  reptococcus  pneumonia. 

Bronchopneumonia. — Bronchopneumonia  has  been  found 
in  every  instance  of  pneumonia  following  measles  save  3, 
namely  in  Autopsy  486,  Autopsy  505  with  lobar  pneumonia 
and  Autopsy  507  with  interstitial  suppurative  pneumonia. 
It  is  not  improbable  that  further  histologic  study  might 
have  demonstrated  small  patches  of  peribronchiolar  pneu- 
monia, for  purulent  bronchitis  was  present  in  the  two  autop- 
sies with  lobar  pneumonia.  This  small  group  of  cases  has  re- 
produced all  of  the  important  features  of  bronchopneumo- 
nia following  influenza.  Hemorrhagic  peribronchiolar  con- 
solidation characterized  by  the  presence  of  small  gray  spots 
clustered  about  terminal  bronchi  upon  a  homogeneously 
red  background  has  been  found  in  5  of  18  instances  of  pneu- 


PATHOLOGY  AND  BACTERIOLOGY   FOLLOWING   MEASLES      341 

monia  with  measles.  Pfeifrer  regarded  this  lesion  as  char- 
acteristic of  the  pneumonia  of  influenza.  Peribronchiolar 
patches  of  consolidation  with  no  surrounding  hemorrhage 
were  found  in  14  instances,  being  recognized  first  by  mi- 
croscopic examination  in  half  of  this  number.  Lobular 
consolidation  occurred  in  11  autopsies  and  peribronchial 
fibrinous  pneumonia  was  present  in  a  third  of  the  autopsies 
on  patients  with  pneumonia  of  measles. 

Bronchial,  peribronchial  and  intraalveolar  hemorrhage 
is  much  more  commonly  associated  with  the  pneumonias  of 
influenza  than  with  the  more  familiar  types  of  acute  bron- 
chopneumonia. Exuded  blood  may  undergo  absorption; 
and  with  bronchopneumonia  which,  persisting  unresolved. 
has  assumed  the  characters  of  a  chronic  lesion,  it  is  com- 
mon to  find  mononuclear  cells  often  in  great  abundance 
filled  with  brown  pigment  derived  from  the  hemoglobin  of 
red  blood  corpuscles. 

Autopsy  439  is  an  example  of  acute  hemorrhagic  broncho- 
pneumonia; there  are  red  lobular  and  confluent  lobular 
patches  of  consolidation  which  upon  the  pleural  surface 
have  a  blue  or  purplish  color.  In  the  dependent  part  of 
the  left  lung  occupying  a  large  part  of  the  lower  lobe  there 
is  lax,  red  consolidation  marked  by  gray  or  yellowish  gray 
spots  of  peribronchiolar  pneumonia  and  in  this  lobe  bronchi 
are  encircled  by  zones  of  hemorrhage.  Pneumococcus  II 
atypical  was  obtained  from  the  lung.  In  Autopsy  444  the 
lesion  has  the  same  hemorrhagic  character  although  lob- 
ular patches  are  in  a  stage  of  grayish  red  hepatization. 
Pneumococcus  II  atypical  has  been  found  in  the  heart's 
blood,  and  with  B.  influenza?  in  lungs  and  bronchus.  Au- 
topsy 441  is  an  example  of  the  occurrence  of  conspicuous 
nodules  of  peribronchiolar  consolidation  in  some  parts  of 
the  lungs  with  the  same  lesion  in  other  parts  on  a  back- 
ground of  hemorrhage.  B.  influenza?  and  S.  aureus  have 
been  found  in  both  lungs  and  bronchi. 


342     PNEUMONIAS  AXli   INFECTIONS  OF   RESPIRATORY  TRACT 

Steinhaus1  states  that  the  pneumonia  of  measles  is  never 
lobular  inflammation  bu1  occurs  in  small  patches  several 
of  which  may  be  Pound  in  a  single  lobule. 

Chronic  fibroid  pneumonia  following  measles  character- 
ized by  cellular  infiltration  and  proliferation  of  the  intersti- 
tial tissue  of  the  lung  has  been  described  by  Bartels,2  Stein- 
haus,   Hart,'  MacCallum8  and  others. 


Vig.  30. — Unresolved  bronchopneumonia  with  measles  showing  new  formation  of  fibrous 
tissue  about  a  bronchus  and  in  immediately  adjacent  alveolar  walls;  partially  obliterated 
alveoli   occur   in    the    peribronchial    fibrous    tissue.     Autopsy    481. 


The  incidence  of  unresolved  bronchopneumonia  among 
instances  of  bronchopneumonia  following  measles  is  higher 
than  that  among  bronchopneumonias  following  influenza. 
There  have  been  6  instances  of  chronic  or  unresolved  bron- 
chopneumonia   among    18   pneumonias    following    measles, 

'Steinhaus:   Ziegler's  I'.eitr.   1901,  xxix,  524. 

-I'.jtrtels:      Virchows   Arch.   f.    path.   Anat.;    xxi. 

3Loc.  cit.,  p.   116. 

■•Hart:    Deutsch.   Arch.    f.    Klin.    Med.,    1904,   Ixxix,    108. 


PATHOLOGY  AND  BACTEEIOLOGY  FOLLOWING  MEASLES      343 

namely  33.3  per  cent.  The  incidence  of  unresolved  broncho- 
pneumonia among  241  autopsies  on  pneumonia  following  in 
fluenza  has  been  21,  namely  8.7  per  cent.  The  essential  fea- 
tures of  this  chronic  lesion  have  been  as  follows:  (a)  chronic 
peribronchiolar  pneumonia  indicated  by  the  presence  of 
firm  nodules  of  peribronchiolar  consolidation  which  have 
considerable  resemblance  to  miliary  tubercles.  Induration  of 


sap 


mm 

■ 

7* 


j*»v *f 


X 


Fig.   31. — Unresolved  bronchopneumonia  with  measles  showing  a  nodule  of  chronic  fibrous 
pneumonia    surrounding   a    respiratory   bronchiole.     Autopsy   481. 

the  nodule  occurs  because  the  walls  of  alveoli  surrounding 
and  adjacent  to  a  respiratory  bronchiole  (Fig.  31)  become 
thickened  and  infiltrated  with  cells  and  there  is  organiza- 
tion of  exudate  within  the  alveoli.  New  formation  of 
fibrous  tissue  (Fig.  32)  occurs  where  the  acute  inflamma- 
tory reaction  of  peribronchiolar  consolidation  is  most  ad- 
vanced (p.  169  and  compare  with  Figs.  3  and  4),  namely, 
about  the  respiratory  bronchiole,   alveolar  duct  and  the 


;U4      PNEUMONIAS  AXU   [NFECTIONS  OF  RESPIRATOR'S   TRACT 

proximal  parts  of  the  infundibula,  disappearing  as  the  dis- 
tal half  of  the  Lnfimdibulum  is  approached.  Distention  of 
the  alveoli  explaining  the  distent  ion  of  the  lung  and  its  fail- 
ure to  collapse  on  section  is  a  noteworthy  feature  of  the 
lesion.  {!>)  Chronic  peribronchial  inflammation  (Fig.  30) 
with  new  formation  of  fibrous  tissue  about  the  smaller  and 
medium-sized  bronchi  extending  into  immediately  adjacent 


F"  TBr  s^F-,  L££  x    r\r    Jb,  WKkJb^ 


Fig.  32. — Unresolved  bronchopneumonia  with  measles  showing  chronic  pneumonia 
about  a  respiratory  bronchiole  and  alveolar  duct;  alveoli  about  the  proximal  parts  of 
three  distended  infundibula  are  filled  with  polynuclear  leucocytes,  whereas  inflammatory 
changes  disappear  as  the  <listal  parts  of  the  infundibula  are  approached.     Autopsy  481. 

alveolar  walls  and  often  associated  with  organization  of 
peribronchial  fibrinous  pneumonia.  (c)  Chronic  lobular 
inflammation  with  changes  similar  to  those  just  cited,  dis- 
tributed throughout  entire  lobules,  (d)  Moderate  thicken- 
ing of  interlobular  septa.  Bronchiectasis  may  be  associ- 
ated with  the  chronic  lesion  (Autopsies  443,  481,  484,  492 
and  496)  but  with  one  exception  (Autopsy  443)  has  been 


PATHOLOGY  AND  BACTERIOLOGY   FOLLOWING   MEASLES       345 


only  moderately  advanced.    Suppurative  pneumonia  with 

abscess  formation  has  occurred  twice  (Autopsies  438  and 
492), 

With  acute  bronchopneumonia  following  measles  the  av- 
erage duration  of  pneumonia,  determined  by  the  date  upon 
which  physical  signs  of  pneumonia  were  first  recognized 
and  in  consequence  subject  to  some  error,  was  seven  days; 
in  instances,  of  chronic  bronchopneumonia  the  average 
duration  of  pneumonia  has  been  fifteen  days. 

The  bacteriology  of  acute  bronchopneumonia  following 
measles  is  shown  in  Table  LXXII. 

Table  LXXII 


WITH    NO 

SPUTUM 

BACTERIA   IN 

BACTERIA    IN 

BACTERIA    IN 

SUPPURATION 

IN  LIFE 

BLOOD  OF  HEART 

LUNGS 

BRONCHI 

Autopsy    390 
439 

441 

Pneum.  II  atyp. 
0 

0 

Pneum.  II  atyp. 

S.  aur. 
B.  inf., 

B.  coli 

B.  inf.,   S.   aur. 

444 

B.  inf. 

Pneum.  II  atyp. 

S.  aur. 
Pneum.  II  atyp. 
B.  inf. 

Pneum.  II  atyp. 
B.  inf. 

453 

Pneum.  I 

Pneum.  I 

Pneum.  I, 
B.  inf. 

With  suppuration : 
442 
491 
507 

8.  hem. 
S.  hem. 
S.  hem. 

S.  hem. 
S.  hem. 
S.  hem. 

S.  hem.,  B.  coli 
S.  hem.,  S.  aur. 

B.  inf.,  S.  hem. 
B.   inf.,   B.   coli 
S.  hem.,  B.  inf., 
S.  aur. 

It  is  noteworthy  that  pneumococci  have  been  recovered 
from  the  heart's  blood  or  lung  in  all  but  1  (Autopsy  441)  of 
5  instances  of  acute  bronchopneumonia  with  no  suppuration 
and  is  doubtless  the  cause  of  this  pneumonia.  Pneumococ- 
cus  II  atypical  has  been  found  in  3  of  4  instances  of  lobar 
pneumonia,  following  measles  and  is  present  in  3  of  these 
5  instances  of  bronchopneumonia. 

Where  suppuration  has  been  found,  hemolytic  strepto- 
cocci have  been  present  in  the  sputum,  in  the  heart's  blood 
and  either  in  the  lungs  (Autopsy  491)  or  in  the  bronchi  (Au- 
topsy 442)  or  in  both  (Autopsy  507).  In  these  instances 
pneumococci  have  not  been  found,  though  in  view  of  the 
readiness  with  which  pneumococci  disappear  from  the  lungs 


34G     PNEUMONIAS  ANH   [NFECTIONS  OF   RESPIRATORS  TRACT 

it  is  possible  thai   they  have  been  the  primary  cause  of 
bronchopneumonia. 

The  bacteriology  of  6  instances  of  unresolved  broncho- 
pneumonia following  measles  is  given  in  Table  LXXIII. 

T.vi'.u-:  LXXIII 


"WITH    NO 

SPUTUM 

BACTERIA    IN 

BACTERIA    IN 

BACTERIA    IN 

SI  PPURA.TION 

IN  LITE 

BLOOD  OF  HEART 

LUNGS 

BRONCHUS 

Autopsy   4  i  ■"■ 

0 

I:,  mli 

B.  inf,  B.coli 

481 

0 

B.  inf. 

B.  inf,  Pneum. 
II,    atyp.,    s. 
hem. 

484 

Pneum. 

IV, 
B.  inf. 

0 

0 

I!,  inf.,  diph- 
theroids 

49G 

1  'llCUIll. 

IV. 

B.  inf. 

0 

0 

B.  inf. 

With  Suppuration : 

Autopsy    438 

B.   inf. 

0 

Pneum.  II 

atyp.,  S.  vir. 
B.  inf.  S.  hem. 

S.  hem,  B.  inf. 

492 

St.  hem., 

B.  inf. 

S.  hem. 

S.  hem.,  Pneum. 
IV,  B.  eoli, 
B.  inf. 

Whereas  with  acute  bronchopneumonia  death  lias  been 
accompanied  and  perhaps  caused  by  bacterial  invasion  of 
the  blood  by  pneumococci  or  streptococci  in  5  of  7  instances, 
with  unresolved  or  chronic  bronchopneumonia  bacteriemia 
has  been  present  only  once,  namely,  in  Autopsy  492  in  which 
with  suppurative  pneumonia  hemolytic  streptococci  have 
entered  the  blood.  It  is  probable  that  pneumococci  have 
likewise  had  an  important  pari  in  the  causation  in  these 
instances  of  bronchopneumonia  which  have  run  a  chronic 
course  but  in  all  save  2  cases  (Autopsies  438  and  492)  have 
disappeared  from  the  lungs.  Pneumococcus  II  atypical  has 
been   found  twice. 

B.  influenza*  has  been  found  in  association  with  acute 
bronchopneumonia  in  the  lungs  in  1  of  6  examinations  and 
in  the  bronchi  in  5  of  6  examinations.  These  figures  indi- 
cate that  it  is  present  in  small  numbers  if  at  all  in  the  con- 
solidated lung  tissue  but  is  relatively  abundant  in  the  bron- 
chi.    With  chronic  bronchopneumonia  B.  influenza'  has  been 


PATHOLOGY  AND  BACTERIOLOGY  FOLLOWING  MEASLES   347 

found  in  every  instance,  in  half  of  the  examinations  of  Lungs 
and  in  all  of  the  examinations  of  bronchi.  In  1  instance 
(Autopsy  481)  B.  influenzae  has  been  found  in  pure  culture 
in  the  lung;  Pneumococcus  II  atypical  has  been  found  in 
the  bronchus  and  has  perhaps  disappeared  from  the  pneu- 
monic lung,  since  this  microorganism  is  often  destroyed 
in  the  late  stages  of  pneumonia  so  that  its  demonstration 
at  autopsy  is  no  longer  possible.  In  1  instance'  15.  influenzas 
found  in  the  bronchus  has  been  the  only  microorganism 
isolated  at  autopsy,  although  the  sputum  during  life  con- 
tained B.  influenza?  and  Pneumococcus  IV. 

Suppurative  Pneumonia. — Suppurative  pneumonia  with 
formation  of  abscesses  has  occurred  in  2  autopsies  with 
pneumonia  following  measles  (Autopsies  438  and  492),  both 
instances  of  chronic  bronchopneumonia.  In  Autopsy  438 
the  lower  and  posterior  part  of  the  left  lower  lobe  has  been 
consolidated  and  has  had  on  section  a  cloudy,  grayish  red 
color;  within  this  area  of  consolidation  and  immediately  be- 
low the  pleural  surface  there  have  been  opaque,  yellow 
spots  where  the  tissue  has  been  softer  than  elsewhere.  Mi- 
croscopic examination  shows  that  the  tissue  has  here  under- 
gone wiclepread  necrosis  so  that  all  nuclear  stain  has  disap- 
peared; at  the  edges  of  the  necrotic  tissue  polynuclear 
leucocytes  are  often  present  in  large  numbers,  but  necrosis 
is  much  more  conspicuous  than  suppuration.  In  the  necrotic 
tissue  and  at  its  edges  streptococci  are  present  in  vast  num- 
bers. Hemolytic  streptococci  have  been  grown  both  from 
the  lung  and  from  the  bronchus,  but  these  have  not  been 
the  only  microorganisms  present,  for  Pneumococcus  II  atyp- 
ical and  S.  viridans  have  been  obtained  from  the  lungs  and 
B.  influenza?  from  lungs  and  bronchus. 

In  Autopsy  492  with  chronic  bronchopneumonia  the  pos- 
terior half  of  the  right  lower  lobe  is  laxly  consolidated,  deep 
red  in  color  and  with  the  cloudy  appearance  often  asso- 
ciated with  streptococcus  pneumonia ;  upon  this  background 
are  peribronchiolar  spots  of  yellow  color,  in  places  well 


348      PNEUMONIAS  ANH   [NFECTIONS  OF   RESPIRATOR'S  TRACT 

seen  below  the  pleura;  in  the  corresponding  pari  of  the  left 
lower  lt'lic  similar  nodules  have  been  converted  into  small 
abscesses  )>y  central  suppuration.  There  is  empyema  on 
the  righl  side,  fibrinopurulenl  pericarditis,  and  purulent 
peritonitis.  Hemolytic  streptococci  had  been  found  in  the 
sputum  three  times,  the  lirst  examination  being  thirteen 
days  before  death.  This  microorganism  is  found  in  pure 
culture  in  the  blood  of  the  heart  and  with  Pneumococci  IV, 
B.  coli  and  B.  influenzae  in  the  lung.  Hemolytic  strepto- 
cocci were  found  in  the  righl  pleural  exudate  and  perito- 
neum. 

The  pneumonias  following  measles  give  opportunity  to 
consider  the  relationship  of  suppurative  interstitial  pneu- 
monia to  unresolved  or  chronic  bronchopneumonia,  which 
is  characterized  by  infiltration  and  proliferation  of  the 
lil irons  tissue  of  the  lung's.  A  number  of  those  who  have 
studied  the  pneumonia  of  measles  have  recognized  that  this 
chronic  interstitial  lesion  is  a  common  sequela  of  measles. 
MacCallum  has  designated  the  lesion  "interstitial  broncho- 
pneumonia," and  has  included  under  this  name  its  acute 
stage  in  which  the  interstitial  character  of  the  lesion  is  not 
more  evident  than  with  other  forms  of  acute  bronchopneu- 
monia. He  has  regarded  S.  hemolyticus  as  the  cause  of 
"interstitial  bronchopneumonia"  following  measles.  A 
review  of  the  autopsies  which  he  has  described  shows  that 
he  has  included  under  the  same  designation  typical  in- 
stances of  interstitial  suppurative  pneumonia  associated 
with  suppurative  lymphangitis.  Instances  of  unresolved, 
chronic  or  "interstitial"  bronchopneumonia  and  of  inter- 
stitial suppurative  pneumonia  which  we  have  observed  after 
measles,  demonstrate  that  the  two  lesions  are  distinguish- 
able both  by  their  anatomic  characters  and  by  their  etiology. 

Three  instances  of  suppurative  interstitial  pneumonia 
occurred  among  the  pneumonias  following  measles  (Au- 
topsies 44l\  4!)1  and  507).  The  lesion  is  characterized  by 
suppuration  of  1  he  interlobular  septa  and  particularly  note- 
worthy   is    the    occurrence    of   suppurative   lymphangitis, 


PATHOLOGY  AND  BACTERIOLOGY    FOLLOWING   MEASLES      849 

lymphatics  being  immensely  dilated  and  distended  with 
purulent  fluid  so  that  their  irregularly  dilated,  bended  ap- 
pearance is  recognizable  upon  the  section  of  the  Lung.  In 
the  group  of  pneumonias  following  measles  this  lesion  has 
not  been  associated  with  unresolved  or  chronic  broncho- 
pneumonia; no  nodular  tubercle-like  foci  of  bronchopneu- 
monia have  been  found  at  autopsy,  and  there  has  been  no 
thickening  of  the  interstitial  tissue.  The  lesion  has  accom- 
panied confluent  lobular  pneumonia  in  2  instances  (Autop- 
sies 442  and  491).  In  the  third  instance  (Autopsy  507) 
there  was  in  the  neighborhood  of  the  suppurative  lesions 
diffuse  consolidation  which  had  the  cloudy,  gray  red  color 
of  streptococcus  pneumonia,  but  this  consolidation  was  not 
lobular  in  distribution. 

The  etiology  of  interstitial  suppurative  pneumonia  es- 
tablished by  study  of  instances  following  influenza  is  con- 
firmed by  Table  LXXII  (p.  345)  showing  the  bacteriology 
of  instances  of  acute  bronchopneumonia  following  measles. 
Pneumococci  are  almost  invariably  found  in  uncomplicated 
instances  of  bronchopneumonia  and  hemolytic  streptococci 
have  been  absent,  whereas  in  3  instances  of  suppurative 
interstitial  pneumonia  hemolytic  streptococci  have  been 
found  in  the  sputum  during  life,  in  pure  culture  in  the  blood 
of  the  heart  and  in  the  lungs  and  bronchus  (missed  in  the 
bronchus  in  one  instance,  Autopsy  507).  In  the  3  instances 
of  the  disease  B.  influenzae  has  been  found  in  the  bronchi. 

Table  LXXIII  shows  that  suppuration  has  accompanied 
unresolved  bronchopneumonia  ("interstitial  bronchopneu- 
monia") in  2  instances  (Autopsies  438  and  492),  but  in 
.these  instances  the  interlobular  tissue  of  the  lung  has  not 
been  the  site  of  suppuration  and  there  has  been  no  suppura- 
tive lymphangitis.  Localized  abscesses  have  been  formed ; 
hemolytic  streptococci,  as  with  abscesses  following  influ- 
enza, have  been  found. 

Empyema  has  occurred  only  5  times  in  association  with 
pneumonia  following  measles  and  in  these  5  instances  has 


350      PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATOE1    TRACT 

been  associated  with  suppurative  pneumonia  caused  by 
hemolytic  streptococci.  In  Autopsy  492  there  was  frbrino- 
purulenl  pleurisy  on  both  sides.  Aspiration  had  been  per- 
formed 3  times  and  at  autopsy  the  righl  pleural  cavity  con- 
tained L50  c.c.  of  purulent  fluid.  In  small  pockets,  corre- 
sponding to  shallow  oval  depressions  upon  the  anterior 
surface  of  the  lung,  fluid  was  walled  off  from  the  general 
cavity.  The  pericardial  cavity  contained  25  c.c.  of  turbid 
yellow  fluid  containing  yellow  Hakes  of  fibrin  and  the  peri- 
toneal cavity  contained  thick  purulent  fluid.  Hemolytic 
streptococci  present  in  the  heart's  blood  and  lung  were  re- 
covered from  the  righl  pleural  cavity  and  Prom  the  peri- 
toneum. Among  3  instances  of  empyema  accompanying 
interstitial  suppurative  pneumonia,  in  1  (Autopsy  491) 
there  were  walled  off  pockets  of  fluid  similar  to  those  just 
described.  Aspiration  of  the  right  pleural  cavity  had  been 
performed  3  times;  at  autopsy  100  c.c.  of  fibrinopurulent 
fluid  was  found  on  the  right  side  and  450  c.c.  on  the  left. 
There  was  general  purulent  peritonitis  and  the  peritoneal 
cavity  contained  350  c.c.  of  thick  yellow  pus.  Hemolytic 
streptococci  were  obtained  from  the  heart's  blood,  right 
lung,  right  pleural  cavity  and  peritoneum. 

Among  4  instances  of  lobar  pneumonia  following  measles 
there  was  serofibrinous  pleurisy  3  times;  in  1  instance  there 
is  no  record  of  pleural  change.  In  1  instance  of  lobar 
pneumonia  (Autopsy  505)  the  right  pleural  cavity  con- 
tained 800  c.c.  of  serofibrinous  exudate  and  the  pericardial 
cavity  contained  510  c.c.  of  opaque,  yellow  seropurulent 
fluid;  Pneumococcus  II  atypical  in  pure  culture  was  ob- 
tained from  the  blood,  lung  and  pleural  and  pericardial 
exudates.  Among  9  instances  of  bronchopneumonia  follow- 
ing measles  there  was  fibrinous  pleurisy  .'!  times,  serofibrin- 
ous 3  times,  and  no  recorded  lesion  of  the  pleura  3  times. 
Empyema,  like  suppurative  pneumonia  following  measles, 
is  in  most  instances,  but  not  constantly,  caused  by  invasion 
of  hemolytic  sf  reptococci. 


PATHOLOGY  AND  BACTERIOLOGY    FOLLOWING    MEASLES      351 

The  foregoing  study  has  shown  thai  pneumonia  which 
lias  followed  measles  lias  reproduced  all  of  the  lesions 
usually  found  after  influenza.  There  is  no  pulmonary 
lesion  peculiar  to  measles.  Lobar  pneumonia  follows  the 
disease  in  some  instances,  but  bronchopneumonia  with 
purulent  bronchitis  is  more  common.  The  same  tendency 
to  hemorrhagic  inflammation  found  with  the  pneumonia  of 
influenza  is  seen  after  measles.  Unresolved  pneumonia 
with  chronic  inflammatory  changes  in  the  interstitial  tissue 
of  the  lung  has  all  of  the  characters  of  the  similar  lesion 
following  influenza  hut  has  been  found  in  a  larger  propor- 
tion of  the  pneumonias  of  measles. 

B.  influenza?  has  been  found  in  the  bronchi  in  14  of  16 
examinations,  namely  in  87.5  per  cent  of  fatal  instances  of 
pneumonia.  In  1  instance  in  which  B.  influenza?  has  not 
been  found  at  autopsy,  it  has  been  isolated  from  the  sputum 
during  life.  It  is  not  improbable  that  B.  influenza?  has 
been  constantly  present  in  the  inflamed  bronchi  both  after 
influenza  and  measles.  It  is  noteworthy  that  the  outbreak 
of  pneumonia  following  measles  has  been  in  part  coincident 
with,  in  part  slightly  subsequent  to,  an  epidemic  of  influ- 
enza which  has  exposed  every  individual  in  the  camp  to  in- 
fection with  this  disease. 

B.  influenza?  has  been  found  in  the  lung  with  the  pneumo- 
nia of  measles  in  7  of  17  examinations,  namely,  in  41.2  per 
cent  of  instances.  The  microorganism  with  measles,  as 
with  influenza,  is  found  in  the  inflamed  lung  only  half  as 
frequently  as  in  the  bronchi.  It  appears  to  be  peculiarly 
adapted  for  multiplication  within  the  bronchial  tubes,  and 
its  isolation  from  the  inflamed  lung  in  less  than  half  of  the 
cases  of  pneumonia  is  perhaps  referable  to  its  presence  in 
the  small  bronchi  and  bronchioles.  The  presence  of  B.  in- 
fluenza? in  the  lungs  in  pure  culture  in  3  instances  at  first 
sight  suggests  that  the  microorganism  produces  pneumo- 
nia, but  a  more  intimate  survey  of  these  cases  gives  little 
support  to  this  view.     In  Autopsy  450  B.  influenza?  has  been 


.>•>_      PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATORY   TRACT 

found  in  pure  culture  in  the  hum-,  bul  Pneumococcus  IV  lias 
been  isolated  Prom  the  blood  of  the  hearl  and  has  been  with 
Little  doubl  the  cause  of  t\  pical  lobar  pneumonia  present  in 
this  instance.  In  Autopsy  486  the  condition  is  almost  iden 
tical,  for  in  the  presence  of  lobar  pneumonia  B.  influenzae 
has  been  round  in  the  lung  in  pure  culture,  bul  Pneumococ- 
cus II  atypical  lias  been  isolated  from  the  pleural  cavity 
and  from  the  bronchus;  in  both  autopsies  the  pneumococci 
which  have  caused  lobar  pneumonia  have  disappeared  from 
thai  part  of  the  consolidated  lung  from  which  a  culture  has 
been  made:  and  here  doubtless  its  invasion  has  been  effec- 
tively resisted  although  it  is  still  present  in  other  organs.  In 
Autopsy  4S1  in  which  B.  influenza?  has  been  isolated  from 
the  lung  in  pure  culture,  the  part  of  pneumococci  in  the 
production  of  the  fatal  disease  is  less  evident;  in  this  in- 
stance. Pneumococcus  II  atypical,  S.  hemolyticus  and  I>.  in- 
fluenzae have  been  isolated  from  the  bronchus. 

The  presence  of  microorganisms  which  have  a  well-es- 
tablished etiologic  relation  to  pneumonia  explains  the  occur- 
rence of  pneumonia  and  makes  unnecessary  the  assumption 
that  B.  influenzae,  which  is  present  in  the  lungs  in  less  than 
half  of  the  instances  examined,  is  essential  to  the  production 
of  the  pneumonic  consolidation.  In  view  of  the  well-recog- 
nized  etiology  of  lobar  pneumonia  we  may  conclude  that 
this  lesion  is  referable  to  the  pneumococci  ( Iuioumococcus 
II  atypical  in  3  instances  and  Pneumococcus  TV  in  1  in- 
stance) isolated  from  the  autopsies  in  which  this  lesion  oc- 
curred. Pneumococcus  (Pneumococcus  IT  atypical  in  3  in- 
stances and  Pneumococcus  T  in  1  instance)  has  been  isolated 
from  the  lungs  or  heart's  blood  in  4  of  5  instances  of  acute 
bronchopneumonia  unaccompanied  by  suppuration.  With 
unresolved  bronchopneumonia  with  no  suppuration,  pneu 
mococci  have  been  in  no  instance  found  in  the  lungs  or  blood, 
though  their  presence  in  the  washed  sputum  during  life  or 
in  the  bronchus  at  autopsy  su.i^'ests  the  possibility  that 
they  may  have  disappeared  from  the  lungs. 


PATHOLOGY  AND   BACTERIOLOGY    FOLLOWING  MEASLES      353 

In  all  instances  in  which  suppuration  lias  occurred 
hemolytic  streptococci  have  been  found  in  the  lungs  or 
blood,  or  in  both.  The  occurrence  of  pneumococci  in  the 
lungs  in  2  of  5  instances  of  suppurative  pneumonia  indi- 
cates that  infection  with  S.  heinolyticus  is  in  some  instances 
at  least  superimposed  upon  acute  bronchopneumonia  caused 
by  pneumococci.  Bronchopneumonia  in  3  instances  has  the 
character  of  that  caused  by  pneumococci.  It  is  probable 
that  the  sequence  of  infection  frequently  observed  after  in- 
fluenza, namely,  bronchial  infection  by  B.  influenzae,  fol- 
lowed by  pneumonia  caused  by  pneumococci,  followed  in 
turn  by  infection  by  hemolytic  streptococci  with  necrosis 
or  suppuration,  is  not  uncommon  after  measles. 

Pneumonia  Associated  with  Acute  Infectious  Diseases 
Other  than  Influenza  and  Measles. — A  small  group  of  au- 
topsies have  been  excluded  from  the  list  of  those  which 
accompanied  the  epidemic  of  influenza,  because  pneumonia 
has  been  associated  with  an  acute  infectious  disease  to 
which  it  is  perhaps  secondary.  These  few  instances  of 
pneumonia,  like  those  following  measles  reproduce  char- 
acters of  the  pneumonia  following  influenza  and  may  be  in 
part  referable  to  influenza  which  has  attacked  an  individual 
suffering  with  typhoid  fever,  mumps  or  scarlet  fever. 

In  2  instances  pneumonia  followed  typhoid  fever  and  ap- 
peared on  September  23  and  26  shortly  after  the  epidemic 
of  influenza  had  become  evident.  In  the  following  autopsy 
there  was  acute  lobar  pneumonia  which  appeared  ten  days 
after  onset  of  typhoid  fever. 

Autopsy  245. — O.  H.,  white,  aged  twenty-one,  a  farmer,  resident  of  Okla- 
homa, had  been  in  military  service  twenty-one  days.  Onset  of  illness  was 
on  September  13  with  chill,  headache,  cough  and  nausea.  The  patient  was 
admitted  two  days  later  with  the  diagnosis  of  acute  bronchitis.  On  Sep- 
tember 20  the  abdomen  was  tense,  the  spleen  was  enlarged  and  rose  spots 
were  present.  Signs  of  lobar  pneumonia  were  found  September  23.  Death 
occurred  September  25,  twelve  days  after  onset  of  typhoid  fever  and  two 
days  after  recognition  of  pneumonia. 

Anatomic  Diagnosis. — Typhoid  fever  with  necrotic  ulcers  in  lower  ileum 
and  in  colon;  hyperplasia  of  ileocecal  lymphatic  nodes;  acute  splenic  tumor; 


354      PNEUMONIAS  A\'l>   [NFECTIONS  OF   I'.KSI'I  KAToi;  V  TII.U  IT 

parenchymatous  degeneration  of  liver  and  kidneys;  acute  lobar  pneumonia 
with  gray  hepatization  in  left  lower  lobe  and  rod  hepatization  and  edema 
in  left  upper  lobe  and  In  righl   lung;  serofibrinous  pleurisy  on  left  side. 

The  lefl  pleura]  cavity  contains  75  c.c.  of  yellowish  gray  turbid  Quid. 
Over  the  lefl  lower  lobe  there  is  a  layer  of  fibrin.  The  upper  half  of  the 
lobe  is  firmly  consolidated,  pinkish  gray  and  coarsely  granular;  the  bronchi 
contain  plugs  of  fibrin.  The  lower  and  posterior  pari  of  the  lower  lobe  is 
consolidated  deep  red  and  edematous.  The  left  upper  lobe  is  edematous  and 
a  layer  in  the  lowermosl  part  in  contact  with  the  lower  lobe  is  deep  red 
ami  consolidated.  The  lefl  lung  weighs  1,490  grms.  The  lower  half  of  the 
righl  upper  lobe  and  the  posterior  border  of  the  lower  is  consolidated  deep 
rod   and  edematous:   the  lung  weighs  970  grms. 

Bacteriologic  examination  shows  that  the  Mood  of  the  ln-art  contains 
Pneumococcus  1 1  atypical. 

The  foregoing  autopsy  is  of  interest  because  typical  lobar 
pneumonia  appears  to  have  spread  from  the  left  lower  lobe, 
where  consolidation  is  firm  and  gray,  to  the  adjacent  part 
of  the  upper  lobe  where  consolidation  is  red  and  edematous. 

The  second  instance  of  pneumonia  following  typhoid 
fever  is  an  instance  of  suppurative  pneumonia  caused  by 
S.  aureus. 

Autopsy  329. — J.  B.,  white,  aged  twenty-two,  laborer,  resident  of  Okla- 
homa, had  been  in  military  service  two  days  before  onset  of  symptoms  of 
typhoid  fever.  He  was  admitted  to  the  hospital  on  August  L'7  and  1'.. 
typhosus  was  found  in  cultures  from  the  Mood  on  September  2  and  3. 
Acme  bronchitis  appeared  on  September  :2f>  when  the  epidemic  of  influ- 
enza had  almost  readied  its  height.  A  diagnosis  of  bronchopneumonia  was 
made  on  the  day  preceding  death,  which  occurred  forty-one  days  after 
onset  of  typhoid  fever  and  eleven   days  after  onset  of  bronchitis. 

Anatomic  Diagnosis. — Typhoid  ulcers  of  ileum;  acute  splenic  tumor; 
acute  bronchopneumonia  with  red  hemorrhagic  peribronchiolar  and  lobular 
consolidation  in  right  lung;  multiple  abscesses  forming  a  circumscribed  group 
in  left  upper  lobe;  purulent  bronchitis. 

The  pleural  cavities  contain  no  excess  of  fluid.  The  lungs  are  voluminous 
and  there  is  interstitial  emphysema.  Below  the  pleura  art'  bluish  red  spots 
of  lobular  consolidation;  in  the  right  upper  lobe  is  a  large  patch  of  red 
consolidation  marked  by  yellowish  gray  spots  in  (dusters.  In  the  external 
and  upper  part  of  the  left  upper  lobe  is  a  patch  of  gray  consolidation 
within  which,  beneath  the  pleura,  there  are  small  abscesses  grouped  to  form 
a  cluster  1.5  cm,  across. 

Bacteriologic  examination  demonstrates  no  microorganisms  in  the  blood 
of  the  heart;  of  two  cultures  from  the  left  lung  one  contains  S.  aureus  in 
pure  culture,  the  other  S.  aureus  and  a   few  colonies  of  Pneumococcus   IV. 


PATHOLOGY  AND  BACTERIOLOGY   FOLLOWING   MEASLES      355 

Cultures  from  the  left  main   bronchus  and    from  the  mucopurulenl   exudate 
in  a  small  bronchus  both  contain  P>.  influenzas,  8.  aureus  and  Pneumococcus  IV. 

Iii  the  foregoing  case  bronchitis  has  appeared  thirty 
days  after  onset  of  typhoid  Cover  on  September  26,  imme- 
diately preceding  the.  height  of  the  epidemic  of  influenza. 
In  association  with  hemorrhagic  bronchopneumonia  there 
is  suppurative  pneumonia  with  small  abscesses  forming  a 
circumscribed  group  below  the  pleura;  there  is  no  em- 
pyema. The  lesion  has  the  characters  of  the  staphylococ- 
cus abscesses  following  influenza,  and  S.  aureus  is  found 
in  association  with  the  lesion;  B.  influenzae  is  identified  in 
two  cultures  from  the  bronchi. 

In  2  instances  pneumonia  was  associated  with  parotitis 
which  was  diagnosed  mumps. 

Autopsy  403. — C.  T.,  colored,  aged  twenty-five,  a  laborer,  resident  of  Ar- 
kansas, had  been  in  military  service  one  month.  Illness  began  September 
27  with  swelling  of  face  behind  jaw  and  difficult  mastication;  the  patient 
was  admitted  to  the  hospital  on  the  same  day  with  the  diagnosis  of  mumps. 
Pneumonic  consolidation  was  recognized  on  October  8.  Death  occurred  Octo- 
ber 13,  sixteen  days  after  onset  of  illness  and  six  days  after  recognition  of 
pneumonia. 

Anatomic  Diagnosis. — Acute  lobar  pneumonia  with  red  and  beginning 
gray  hepatization  of  lower  and  parts  of  upper  and  middle  right  lobes;  acute 
bronchopneumonia  with  lobular  consolidation  in  left  lung;  purulent  bron- 
chitis;  bronchiectasis  in  left  lung. 

The  lower  lobe  of  the  right  lung  with  the  exception  of  the  anterior  and 
basal  edge  is  firmly  consolidated;  the  posterior  part  of  the  middle  lobe  and 
a  small  corner  at  the  posterior  and  lower  part  of  the  upper  lobe  is  similarly 
consolidated.  The  consolidated  tissue  is  gray  and  coarsely  granular  on 
section.  The  remainder  of  the  lung  is  dry  and  voluminous,  and  the  bronchi 
contain  purulent  fluid.  The  left  lung  contains  red  and  gray  patches  of 
consolidation,  from  0.2  to  3  cm.  across.  Bronchi  contain  purulent  fluid  and 
in  the  lowermost  parts  of  both  upper  and  lower  lobes  are  moderately 
dilated. 

Bacteriologic  examination  shows  that  the  blood  of  the  heart  contains 
Pneumococcus  III. 

It  is  noteworthy  that  there  was  in  this  case,  as  in  many 
instances  of  influenza,  both  lobar  and  bronchopneumonia. 
Purulent  bronchitis  was  present  and  there  was  bronchiec- 
tasis throughout  one  lunsr. 


356      PNEUMONIAS  AND   INFECTIONS  OF  RESPIRATORY  TRACT 

In  the  following  case  the  diagnosis  of  mumps  may  be 
questioned  since  the  lesion  of  the  parotid  has  characters  of 
terminal  suppurative  parotitis. 

Autopsy  417. — H.W.D.,  white,  aged  twenty-four,  a  farmer,  resident  of 
Oklahoma,  had  been  in  military  Bervice  one  month.  He  said  thai  he  had 
had  pneumonia  four  times.     He  was  admitted  to  the  hospital  delirious  and 

the  diagnosis  of  lobar  pneumonia  was  made.  Parotitis  regarded  as  mumps 
appeared   five   days  before  death   and   suppuration   occurred   on   the   righl 

si.le  of  the  face.  Death  of  the  patient  occurred  thirteen  days  after  admis- 
sion to  the  hospital. 

Anatomic  Diagnosis. — Acute  bronchopneumonia  with  lobular  consolida- 
tion in  both  lungs;  suppurative  pneumonia  with  necrosis  and  beginning  ab- 
scess formation  in  left  lung;  purulent  pleurisy  in  left  side;  purulent  bron- 
chitis; bronchiectasis;  acute  parotitis. 

The  left  pleural  cavity  contains  100  c.c.  of  purulent  fluid  of  creamy  con- 
sistence. The  left  lung  is  voluminous  and  bound  to  the  chest  wall  in  places. 
There  are  numerous  patches  of  lobular  consolidation.  At  the  apex  of  the 
lung  there  is  a  large  area  of  consolidation,  7  cm.  across,  where  the  tissue 
is  cloudy  gray  and  soft  in  consistence.  In  the  upper  lobe  is  a  well-defined 
patch  of  grayish  yellow  color,  (>  by  2  cm.,  with  opaque  yellow  edges;  puru- 
lent fluid  escapes  from  the  cut  surface.  Bronchi  throughout  the  lung  are 
widely  dilated  and  contain  purulent  fluid.  The  right  lung  is  voluminous 
and  contains  lobular  patches  of  consolidation;  bronchi  of  this  lung  are  widely 
dilated. 

Bacteriologic  examination  shows  the  presence  of  hemolytic  streptococci 
in  the  blood  of  the  heart;  hemolytic  streptococci  and  B.  influenzae  in  the 
lung,  and  hemolytic  streptococci,  B.  influenza?  and  S.  aureus  in  a  main 
bronchus. 

In  association  with  bronchopneumonia  there  have  been 
necrosis  and  beginning  abscess  formation  with  empyema, 
the  suppurative  lesions  being  caused  by  hemolytic  strep- 
tococci which  had  finally  entered  the  blood  stream.  There 
was  purulent  bronchitis,  and  the  lungs  bad  the  voluminous 
character  often  associated  with  this  lesion;  there  was  be- 
ginning bronchiectasis.  B.  influenzae  was  obtained  both 
from  the  lung  and  from  the  bronchus. 

In  2  instances  (Autopsies  323  and  335)  the  diagnosis  of 
scarlet  fever  was  made  in  patients  suffering  with  pneu- 
monia following  influenza.  These  lesions  have  been  in- 
cluded in  the  list  of  influenzal  pneumonias.  In  the  follow- 
ing instance  the  patient  was  admitted  with  scarlet  fever, 


PATHOLOGY  AND  BACTERIOLOGY   FOLLOWING   MEASLES       00/ 

later  developed  acute  follicular  tonsillitis,  and  finally  sup- 
purative pneumonia  caused  by  hemolytic  streptococcus. 

Autopsy  311. — E.  J.,  white,  aged  twenty-two,  a  tinsmith  ami  automobile 
repairer,  resident  of  Arkansas,  had  been  in  military  service  three  months. 
Onset  of  illness  was  on  September  18  with  headache  and  sore  throat.  The 
patient  was  admitted  September  24  with  the  diagnosis  of  scarlet  fever;  two 
days  later  there  was  acute  follicular  tonsillitis.  Pneumonic  consolidation 
on  the  right  side  was  recognized  October  2,  three  days  before  death. 

Anatomic  Diagnosis. — Acute  suppurative  pneumonia  with  three  small  ab- 
scesses below  pleura  of  right  lower  lobe;  acute  fibrinopurulent  pleurisy  on 
both  sides;   serous  pericarditis. 

The  right  pleural  cavity  contains  1500  c.c.  of  turbid,  dirty  yellow  fluid 
containing  masses  of  fibrin;  the  left  cavity  has  500  c.c.  of  similar  contents. 
The  pericardium  contains  30  c.c.  of  turbid  fluid  containing  a  small  quantity 
of  fibrin;  there  are  ecchymoses  below  the  epieardium.  The  right  lung  is  col- 
lapsed and  in  the  lower  lobe  contains  three  small  subpleural  abscesses,  the 
largest  of  which  is  1.5  cm.  across. 

Bacteriologic  examination  shows  the  presence  of  hemolytic  streptococci  in 
pure  culture  in  the  blood  of  the  heart  and  in  the  right  lung.  From  the 
right  main  bronchus  are  obtained  hemolytic  streptococci,  B.  influenza?, 
Pneumococcus  IV  and  a  few  staphylococci. 

In  this  instance  there  has  been  infection  with  strepto- 
coccus which  is  a  common  sequela  of  scarlet  fever.  In  the 
absence  of  evidence  of  bronchopneumonia  there  has  been 
abscess  formation  below  the  pleura  with  empyema  and 
pericarditis.     B.  influenzae  has  been  found  in  the  bronchus. 

The  pneumonias  found  in  association  with  measles  re- 
produce the  characters  of  the  pneumonias  described  in  as- 
sociation with  influenza.  Particularly  noteworthy  is  the 
occurrence  of  lobar  pneumonia,  hemorrhagic  peribronchio- 
lar pneumonia,  interstitial  suppurative  pneumonia,  severe 
bronchitis  with  bronchiectasis  and  unresolved  bronchopneu- 
monia. In  the  presence  of  an  epidemic  of  influenza  at- 
tacking more  than  one  fourth  of  the  population  of  a  camp, 
those  suffering  with  diseases,  such  as  measles,  typhoid 
fever,  mumps,  etc.,  are  unlikely  to  escape  entirely,  and  it 
is  probable  that  the  tendency  to  the  occurrence  of  pneu- 
monia present  in  association  with  these  diseases  will  be 
increased.     The  close  resemblance  between  the  pneumonias 


358      PNEUMONIAS  AND   INFECTIONS  OF   RESPIRATOR'S  TRACT 


which  we  have  found  with  the  diseases  mentioned,  on  the 
cm'  hand,  and  the  pneumonias  of  influenza  on  the  other, 
l>oth  being  characterized  by  the  occurrence  of  hemorrhagic, 
suppurative  and  chronic  pulmonary  lesions,  indicates  thai 
influenza  has  had  a  part  in  the  production  of  the  pneumonia 
found  with  measles  and  some  other  infectious  diseases  dur- 
ing the  progress  of  the  epidemic  of  influenza. 


CHAPTER  VII 

SUMMARY    OF    THE    INVESTIGATION    AND    CON- 
CLUSIONS REACHED 

Eugene  L.  Opie,  M.D. 

There  is  no  reason  for  believing  that  the  influenza  which 
prevailed  in  this  country  differed  in  any  essential  feature 
from  that  of  previous  epidemics  and  particularly  of  the 
pandemic  of  1889-90.  Our  studies  have  shown  that  an  or- 
ganism with  the  morphologic  and  cultural  characters  of  B. 
influenza?  of  Pfeiffer  has  been  constantly  found  in  associa- 
tion with  the  disease,  and  so  frequently  demonstrated  in 
association  with  its  pulmonary  complications  that  there  is 
little  doubt  of  its  constant  presence.  The  bronchial  and 
pulmonary  complications  of  influenza  present  characters 
which,  while  varied,  are  not  usually  observed  in  the  absence 
of  epidemic  influenza,  and  in  this  pandemic  agree  with  those 
of  the  former  pandemic  so  far  as  it  is  possible  to  determine 
from  the  descriptions  available. 

Especially  noteworthy  is  the  severity  of  the  changes 
within  the  bronchial  passages.  Clinical  studies  have  shown 
that  purulent  bronchitis  has  occurred  in  36  per  cent  of  in- 
stances of  influenza.  The  sputum  with  this  condition  has 
contained  B.  influenza?  in  all  instances,  but  although  there 
were  no  signs  of  pneumonia  it  has  been  constantly  associ- 
ated with  other  microorganisms,  namely,  pneumococci  (in 
11  of  13  instances),  S.  hemolyticus,  S.  viridans,  M.  catar- 
rhalis,  etc. 

Identification  of  the  bacteria  which  have  been  present 
in  the  bronchi  of  those  dead  with  pneumonia  following  in- 
fluenza have  determined  what  microorganisms  have  pene- 
trated into  the  lower  respiratory  passages.     B.  influenzae 

359 


360      PNEUMONIAS  AND   [NFECTIONS  OF  RESPIRATOR!    TRACT 

lias  been  found  so  frequently  (80  per  cent)  thai  there  is 
good  reason  to  believe  thai  it  lias  been  constantly  presenl 
ami  has  not  been  isolated  in  every  instance  because  it  1ms 
been  overgrown  by  other  microorganisms  on  the  plates  or 
after  long  continued  illness  has  disappeared  from  the  bron- 
chi. .Mixed  infections  of  B.  influenzae  and  other  microor- 
ganisms are  constantly  found  in  the  inflamed  bronchi;  com- 
binations of  I>.  influenza1  and  pneumococci,  B.  influenzae  and 
hemolytic  streptococci  or  these  combinations  with  staphylo- 
cocci or  the  four  organisms  together  are  common.  Other 
microorganisms  such  as  B.  coli,  S.  viridans,  M.  catarrhalis 
and  diphtheroid  bacilli  are  not  infrequently  associated  with 
those  winch  have  been  mentioned. 

Purulent  bronchitis  has  been  found  in  137  of  241  autop- 
sies; its  bacteriology  differs  in  no  respect  from  that  which 
has  just  been  described  and  indeed  no  line  can  be  drawn 
between  this  condition  and  the  bronchitis  invariably  pres- 
ent with  the  pneumonias  of  influenza.  Other  evidence  of 
profound  injury  to  the  bronchi  is  the  frequent  occurrence 
of  hemorrhage  in  a  zone  ensheathing  the  smaller  bronchi, 
and  the  common  occurrence  of  bronchiectasis  when  the 
fatal  disease  lias  lasted  more  than  two  or  three  weeks. 

Microscojoic  study  demonstrates  that  the  changes  in  the 
bronchial  walls  are  such  as  destroy  the  defences  against 
invasion  by  microorganisms.  The  bronchial  epithelium 
undergoes  destruction  which  is  not  infrequently  limited  to 
the  superficial  ciliated  cells,  but  often  complete  loss  of  epi- 
thelium occurs.  The  mucous  glands  of  the  larger  bronchi 
exhibit  a  special  susceptibility  to  injury,  and  in  the  early 
stages  of  the  lesion  profound  degenerative  changes  are 
found  in  the  secreting  cells,  whereas  at  a  later  stage  chronic 
inflammatory  changes  are  almost  invariably  present. 

Pneumonia  following  influenza  is  in  most  instances  bron- 
chopneumonia, bid  typical  lobar  pneumonia  has  been  found 
in  autopsies  representing  40.7  per  cent  of  pneumonias  of  in- 
fluenza.   Lobar  pneumonia  is  frequently  accompanied  by 


SUMMARY  OF   I INVESTIGATION  AM)  CONCLUSIONS  361 

purulent  bronchitis,  and  in  a  considerable  number  of  au- 
topsies (34  of  98  with  lobar  pneumonia)  lobar  and  broncho- 
pneumonia have  occurred  in  the  same  individual. 

Statistics  based  upon  the  clinical  diagnosis  of  lobar  and 
bronchopneumonia  following  influenza  are  so  inaccurate 
that  they  have  little  if  any  value.  Notwithstanding  care- 
ful study  of  the  symptomatology  of  the  disease,  lobar 
and  bronchopneumonia  following  influenza  are  not  ac- 
curately distinguishable  by  the  means  usually  employed, 
and  an  erroneous  diagnosis  has  been  recorded  on  the  pa- 
tient's history  in  36.6  per  cent  of  227  fatal  cases  with  au- 
topsy. A  diagnosis  of  suppurative  pneumonia  is  rarely  if 
ever  made.  The  difficulties  of  diagnosis  are  in  part  ex- 
plained by  the  frequent  association  of  lobar  pneumonia 
with  purulent  bronchitis,  with  bronchopneumonia  or  with 
both,  and  by  the  occurrence  of  bronchopneumonia  with  con- 
fluent lobular  consolidation  involving  a  large  part  of  a  lobe 
or  whole  lobes. 

There  are  many  defects  in  the  present  knowledge  of 
the  symptomatology  of  the  pneumonias  under  considera- 
tion. The  symptoms  of  suppurative  pneumonia  are  not 
clearly  defined.  Many  of  these  deficiencies  might  be  sup- 
plied by  further  application  of  the  time-honored  method  of 
comparing  the  clinical  course  of  the  disease  with  the 
changes  found  at  autopsies,  supplemented  by  bacteriologic 
studies  made  during  life  and  confirmed  after  death. 

With  peribronchial  pneumonia  bronchi  of  medium  size, 
on  the  cut  surface  of  the  lung,  are  surrounded  by  sharply 
defined  zones  of  pneumonic  consolidation  perhaps  0.5  em. 
in  radius,  and  this  lesion  furnishes  conclusive  proof  that 
the  inflammatory  process  can  extend  directly  through  the 
bronchial  wall  reaching  all  alveoli  within  a  limited  dis- 
tance for  these  alveoli  bear  no  relation  to  the  distribution 
of  the  terminal  bronchi  of  the  affected  bronchus.  This 
peribronchial  pneumonia  is  usually  characterized  by  fibrin- 
ous exudate,  and  jmeumococcus  has  been  found  either  iii 


362      PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATOR'S  TRACT 

the  blood  of  the  heart  or  in  the  lung  in  all  of  (i  instances  in 
which  peribronchial  consolidation  has  been  recognized  a1 

autopsy;  in  half  of  these  autopsies  Pneumococcus  Type  11 
has  been  isolated  and  this  relationship  is  especially  note- 
worthy because  Type  II  has  been  uncommonly  associated 
w  it  h  t  he  pneumonias  of  influenza. 

Lobar  Pneumonia. — The  distribution  of  lobar  pneumonia 
lias  repeatedly  furnished  evidence  that  the  process  spreads 
like  the  peribronchial  lesion  directly  through  the  tissue  of 
the  lung  and  is  not  necessarily  disseminated  by  way  of  the 
bronchia]  tree.  PneumoCOCC]  doubtless  enter  the  lung  by 
way  of  the  bronchi;  the  occurrence  of  lobar  pneumonia  in 
frequent  association  with  influenza  which  exhibits  a  pecu- 
liar capacity  to  destroy  the  defences  of  the  lower  respira- 
tory passages  is  in  harmony  with  this  view.  The  presence 
of  pneumococci  in  the  blood  furnishes  no  evidence  that 
infection  is  hematogenous,  for  bacterial  infections,  par- 
ticularly at  their  onset,  are  frequently  accompanied  by  bac- 
teremia. The  wave-like  spread  of  lobar  pneumonia  may  be 
indicated  by  a  narrow  zone  of  red  hepatization  separating  a 
large  patch  of  firm,  gray  consolidation  from  engorged  but 
air  containing  lung  tissue.  A  semicircular  patch  of  con- 
solidation not  infrequently  extends  from  the  left  lower  lobe 
into  the  upper  lobe  at  the  site  where  the  interlobular  cleft 
is  absent.  This  patch  may  be  firm  and  gray  in  continuity 
with  similar  consolidation  in  the  lower  lobe  but  surrounded 
over  its  convex  surface  by  a  zone  of  red  hepatization. 

There  is  no  reason  to  doubt  that  the  lobar  pneumonia 
which  Ave  have  found  with  influenza  has  been  constantly 
caused  by  pneumococci.  We  have  encountered  no  instance 
of  lobar  pneumonia  caused  by  the  capsulated  bacillus  of 
Friedlander.  The  incidence  of  different  types  of  pneumo- 
cocci in  the  lung  with  lobar  pneumonia  has  been  as  follows: 
Type  IV,  32.4  per  cent;  Type  II,  atypical,  26.5  per  cent; 
Type  III,  L7.6  per  cent;  Type  II,  5.9  per  cent;  Type  I,  2.9 
per  cent;  no  pneumococci  found  14.7  per  cent.     It  is  note- 


SUMMARY  OF  INVESTIGATION   AND  CONCLUSIONS  363 

worthy  that  this  distribution  of  types  is  in  sharp  contrast 
with  the  lobar  pneumonia  of  civil  life  with  which  Types  I 
and  II  constitute  the  cause  of  two-thirds  of  all  instances, 
and  is  in  agreement  with  the  etiology  of  the  pneumonias 
found  in  an  army  camp  (Punston)  in  the  absence  of  in- 
fluenza in  epidemic  proportion. 

Bronchopneumonia. — Bronchopneumonia  is  associated 
with  intense  bronchitis  penetrating  to  the  finest  bronchioles 
and  is  characterized  by  consolidation  distributed  in  such 
definite  relation  to  the  bronchial  tree  that  dissemination 
of  the  inflammatory  irritant  by  way  of  the  bronchi  is  evi- 
dent. Consolidation  occurs  (a)  in  foci  affecting  alveoli 
in  immediate  proximity  to  the  respiratory  bronchioles  and 
in  consequence  clustered  about  the  terminal  bronchi,  the 
intervening  alveolar  tissue  containing  air;  (b)  in  foci  of 
the  same  character  surrounded  by  intraalveolar  hemor- 
rhage whch  occupies  all  alveolar  tissue  between  adjacent 
foci;  (c)  throughout  whole  lobules  or  groups  of  lobules, 
intervening  lobules  being  unaffected ;  (d)  surrounding  bron- 
chi of  medium  size  like  a  sheath. 

The  lobar  pneumonia  of  influenza  is  characterized  by 
frequent  association  with  purulent  bronchitis  and  broncho- 
pneumonia. The  bronchopneumonia  of  influenza  exhibits 
characters  which  serve  to  distinguish  it  from  other  forms 
of  bronchopneumonia;  (a)  The  associated  lesions  of  the 
bronchi  are  unusually  severe ;  purulent  exudate  accumulates 
within  the  lumen  and  the  lining  membrane  is  destroyed. 
(b)  Pneumonia  is  frequently  hemorrhagic  with  accumula- 
tion of  blood  within  the  alveoli  and  within  and  surrounding 
the  bronchi,  (c)  There  is  unusual  susceptibility  of  the  in- 
jured bronchi  and  of  the  pulmonary  tissue  to  secondary  in- 
vasion by  streptococci  and  staphylococci  with  consequent 
necrosis  and  suppuration,  (d)  Bronchiectasis  frequently 
accompanies  bronchitis,  (c)  Bronchopneumonia  frequently 
fails  to  resolve  and  the  lesion  assumes  the  character  of  a 
chronic  pneumonia. 


364      PNEUMONIAS  ANH   INFECTIONS  OF  RESPIRATOE'S  TRACT 

AYith  bronchopneumonia  pneumococci  are  found  with  B. 
influenzae  in  the  bronchi  and  lungs  in  nearly  half  and  in 
the  blood  in  approximately  one-third  of  instances  of  the 
disease,  1  m t  hemolytic  streptococci,  staphylococci,  S.  viri- 

dans,  P>.  coli,  M.  catarrhalis  and  other  microorganisms  are 
very  frequently  found  in  various  combinations:  they  un- 
doubtedly have  a  pari  in  the  production  of  the  lesion. 
Mixed  in  feet  ion  of  the  lung  and  even  of  the  blood  with  pneu- 
mococci and  hemolytic  streptococci  is  often  found,  and 
study  of  the  sputum  during  life  has  repeatedly  shown  that 
pneumococci  alone  are  present  shortly  after  the  onset  of 
the  disease,  whereas  hemolytic  streptococci  appear  later 
or  are  first  discovered  at  autopsy.  In  such  instances  pneu- 
mococci have  not  infrequently  disappeared  from  the  lung 
and  at  autopsy  hemolytic  streptococci  alone  are  demon- 
strable. 

The  part  which  B.  influenza'  has  in  the  production  of 
bronchopneumonia  is  of  great  interest.  This  microorgan- 
ism is  demonstrable  by  cultures  in  at  least  three-fourths 
of  all  instances  of  bronchopneumonia  but  is  obtained  from 
the  inflamed  lung  tissue  in  less  than  half.  In  no  instance 
of  pneumonia  have  we  found  B.  influenzae  unassociated  with 
other  microorganisms,  whereas  repeatedly  pneumococci 
have  been  the  only  microorganism  demonstrable  in  the 
lung  and  very  frequently  the  only  organism  present  in  the 
blood.  In  view  of  the  difficulty  of  demonstrating  the  mi- 
croorganism in  plates  overgrown  by  other  bacteria,  it  is 
probable  that  its  incidence  in  the  bronchi  is  much  higher, 
if  it  is  not  constantly  present,  whereas  its  isolation  from 
the  lung  is  in  part  referable  to  its  presence  in  the  small 
bronchi  where  it  can  he  readily  demonstrated  by  cultures 
or  by  microscopic  preparations.  We  have  been  almost  uni- 
formly unsuccessful  in  demonstrating  the  microorganism  in 
the  alveoli  of  the  lung.     Goodpasture  and  Burnett,1  who 

'Goodpasture,  E,  AW.  and  Burnett,  P.  T,.:  The  Pathology  of  Pneumonia  Accompany- 
ing  Influenza,   U.    S.   Nav.   Med.    Bull.,    1919,   xiii,  No.   2,   P.   21. 


SUMMARY  OF  INVESTIGATION  ANT)  CONCLUSIONS  365 

have  devised  a  special  method  For  the  demonstration  of  B. 
influenzae  in  tissues,  have  found  few  of  these  microorgan- 
isms in  the  alveoli  of  the  lungs. 

Pneumonia  characterized  by  the  occurrence  of  small 
(peribronchiolar)  spots  of  leukocytic  pneumonia  upon  an 
almost  homogeneous  background  of  intraalveolar  hemor- 
rhage, was  regarded  by  Pfeiffer  as  the  characteristic  lesion 
produced  by  his  microorganism.  B.  influenza1  in  our  autop- 
sies has  borne  the  same  relation  to  this  lesion  which  it  has 
exhibited  to  other  forms  of  bronchopneumonia;  pneumo- 
cocci  have  been  present  with  approximately  the  same  fre- 
quency and  hemolytic  streptococci  have  often  been  found. 

Streptococcus  Pneumonia. — The  occurrence  of  strepto- 
coccus pneumonia  with  suppuration  occurring  in  the  trail 
of  influenza  was  frequently  observed  during  the  pandemic 
of  1889-90.  It  is  now  well  recognized  that  the  streptococcus 
concerned  is  one  capable  of  causing  hemolysis.  Suppura- 
tive pneumonia  referable  to  hemolytic  streptococci  is  of 
two  types  which  are  readily  separable  by  their  anatomic 
characters:  (a)  One  or  several  abscesses  are  situated  below 
the  pleura  and  accompanied  by  empyema.  Their  relation  to 
severe  lesions  of  the  bronchi  is  not  infrequently  demon- 
strable, for  a  destructive  lesion  of  the  bronchial  wall  has 
penetrated  into  the  surrounding  alveolar  tissue  so  that  ne- 
crosis of  tissue  and  subsequent  abscess  formation  occur  r 
continuity  with  the  bronchial  lumen.  The  localization  of 
the  abscess  below  the  pleura  is  referable  to  the  greater 
severity  of  the  lesions  of  the  small  bronchi  which  are  most 
numerous  at  the  periphery,  to  the  greater  severity  of  these 
bronchial  lesions  at  the  bases  of  the  lung,  and  to  the  rela- 
tion of  lymphatics  within  the  interior  of  the  lung  to  those 
of  the  pleura.  It  is  not  improbable  that  stasis  of  lymph 
caused  by  thrombosis  of  the  lymphatics  has  a  part  in  the 
production  of  abscess.  Preceding  or  accompanying  ab- 
scess formation,  the  lung  tissue  undergoes  consolidation  and 
in  a  wide  area  about  the  abscess  has  a  homogeneous  gray 


366      PNEUMONIAS  A.ND   [NFECTIONS  OF   RESPIRATOR?  TRACT 

cloudy  appearance  occasionally  mottled  by  opaque  patches 
of  necrosis.  (M  [nterstitial  suppurative  pneumonia  is  a 
lesion  nol  infrequently  found  in  association  with  influenza 
(ill  times  among  241  autopsies)  and  rarely,  if  ever,  seen  in 
its  absence.  There  are  few  references  to  this  lesion  in  the 
pathologic  literature  of  the  English  language  and  those  of 
German  origin  in  great  part  refer  to  the  period  of  the  pan- 
demic of  L889-90.  The  lesion  is  essentially  suppurative 
lymphangitis,  and  both  thrombosis  and  suppuration  of  the 
lymphatics  are  widespread  throughoul  the  affected  lung.  In 
proximity  to  the  inflamed  lymphatics  and  the  surrounding 
interstitial  septa,  lung  tissue  throughout  parts  of  the  lobes 
or  even  throughout  a  whole  (lower)  lobe  lias  undergone 
consolidation  and  lias  the  gray,  cloudy  appearance  of  strep- 
tococcus pneumonia. 

Staphylococcus  Pneumonia. — Abscesses  produced  by 
staphylococci  differ  in  anatomic  characters  and  sequelae 
from  those  caused  by  hemolytic  streptococci.  Small  ab- 
scesses occur  in  one  or  several  localized  clusters;  these  ab- 
scesses are  grouped  about  a  bronchus  and  have  their  origin 
in  its  terminal  branches.  This  relation  may  be  readily  dem- 
onstrated in  microscopic  sections.  The  lesion  tends  to  re- 
main localized  and  pneumonic  consolidation  is  limited  to 
the  immediate  neighborhood  of  the  group  of  abscesses. 
There  is  no  lymphangitis  and  the  lesion  is  not  accompanied 
by  empyema. 

Empyema. — Empyema  is  almost  invariably  associated 
with  suppurative  pneumonia  caused  by  hemolytic  strep- 
tococci. Among  our  autopsies  purulent  fluid  has  been 
found  in  the  pleural  cavity  55  times;  it  occurred  1.1  times 
among  17s  instances  of  lobar  or  bronchopneumonia  and  50 
times  among  60  instances  of  suppurative  pneumonia  re- 
ferable to  S.  hemolyticus.  In  our  experience  hemolytic 
streptococci  and  pneumococci  are  the  only  microorganisms 
which  exhibit  a  noteworthy  capacity  to  penetrate  from  the 
lung  to  Ihc  pleural  cavity.    We  have  not  found  nonhemo- 


SUMMARY  OF  [INVESTIGATION  AM)  CONCLUSIONS  367 

lytic  streptococci  (e.g.,  S.  viridans)  in  association  with  em- 
pyema. 

Staphylococcus  has  failed  to  invade  the  pleural  cavity 
even  when  a  pulmonary  abscess  has  been  present  below  the 
pleura,  and  in  the  only  instances  in  which  staphylococci 
have  been  isolated  from  the  pleural  cavity  thoracotomy  had 
been  performed  for  empyema  caused  by  hemolytic  strep- 
tococci (2  instances)  or  an  abscess  communicating  with  both 
bronchus  and  pleura.  B.  influenzae  has  been  found  in  the 
pleural  cavity  with  empyema  only  once  and  in  this  instance 
cannot  be  regarded  as  the  cause  of  the  lesion,  for  it  has 
accompanied  hemolytic  streptococci. 

Bronchiectasis. — Bronchiectasis  has  been  frequently 
found  as  a  sequela  of  the  severe  bronchitis  of  influenza  and 
there  has  been  abundant  opportunity  to  study  the  lesion 
in  process  of  development.  These  observations  have  fur- 
nished a  satisfactory  explanation  of  its  etiology  and  patho- 
genesis. Infection  of  the  bronchi  by  B.  influenzae,  accom- 
panied by  a  variety  of  other  microorganisms,  notably  hem- 
olytic streptococci  and  staphylococci,  has  caused  profound 
changes  in  the  bronchial  wall  beginning  with  destruction 
of  the  epithelial  surface,  and  followed  by  necrosis  pene- 
trating partially  or  completely  through  the  wTall  and  oc- 
casionally extending  into  the  surrounding  alveolar  tissue. 
The  difference  between  the  atmospheric  pressure  within 
the  bronchi  and  the  lower  inspiratory  pressure  within  the 
surrounding  alveoli,  accentuated  by  forced  inspiration  at 
intervals  and  by  occlusion  of  the  bronchioles  with  mucopur- 
ulent exudate,  ruptures  the  necrotic  tissue  and  produces 
longitudinal  fissures  which  are  recognizable  both  macro- 
scopically  and  microscopically.  In  consequence  of  the  sep- 
aration of  the  edges  of  these  fissures  by  intrabronchial  pres- 
sure the  circumference  is  increased.  These  rents  in  the 
wall  are  limited  and  partially  healed  by  fibrinous  pneu- 
monia about  them,  by  new  formation  of  fibrous  tissue  from 
the  bronchial  wall,  and  adjacent  interalveolar  septa,  by 


368      PNEUMONIAS  AX1>  [NFECTIONS  OF  RESPIRATOR'S  TRACT 

organization  of  fibrin  within  adjacent  alveoli  and  finally  by 
growth  of  epithelium  over  the  denuded  surfaces. 

Bronchitis  caused  by  B.  influenzae  and  pyogenic  micro- 
cocci with  necrosis  of  the  bronchi  wall  is  the  essential  fac- 
tor in  the  production  of  bronchiectasis,  but  advanced  bron- 
chiectasis is  found  only  in  those  individuals  who  have  sur- 
vived the  onset  of  illness  during  several  weeks,  for  dila- 
tation under  the  influence  of  positive  intrabronchial  and 
negative  extrabronchial  pressure  occurs  slowly. 

Unresolved  Bronchopneumonia. — Unresolved  lobar  pneu- 
monia lias  not  been  recognized  among  instances  of  pneu- 
monia following  influenza,  but  unresolved  bronchopneu- 
monia is  of  frequent  occurrence  and  lias  well  definable  gross 
and  microscopic  characters.  There  are  purulent  bronchitis, 
bronchiectasis  and  distention  of  the  lung  tissue,  so  that  it 
fails  to  collapse;  particularly  characteristic  are  the  indur- 
ated foci  of  peribronchiolar  pneumonia,  which  being  firm 
and  sharply  defined,  have  the  appearance  of  miliary  tu- 
bercles. When  the  process  is  sufficiently  long  continued 
there  are  recognizable  patches  of  fibroid  pneumonia.  ]\li- 
croscopic  examination  shows  that  the  lesion  is  characterize* I 
by  organization  of  fibrinous  exudate  not  only  within  the 
alveoli  but  within  bronchioles  as  well,  and  by  thickening 
of  the  alveolar  walls,  thickening  of  fibrous  tissue  about 
the  bronchi  and  blood  vessels,  and  thickening  of  interstitial 
septa.  These  changes  may  occur  as  peribronchiolar  patches 
of  consolidation,  producing  tubercle-like  nodules,  or  may  in- 
volve areas  of  hemorrhagic  peribronchiolar  or  of  lobular 
consolidation,  or  may  be  limited  to  the  immediate  neigh- 
borhood of  bronchi  (peribronchial). 

Xo  peculiarity  of  the  bacterial  flora  of  the  bronchi  or  of 
the  lung  offers  a  satisfactory  explanation  of  the  failure  of 
pneumonic  exudate  to  resolve.  Mixed  infections  have  been 
common  and  S.  hemolyticus,  staphylococci,  pneumococci, 
S.  viridans,  B.  coli,  etc.,  have  been  found  in  association  with 
B.  influenza'  but  the  incidence  of  these  microorganisms  has 


SUMMARY  OF   [INVESTIGATION  AND  CONCLUSIONS  369 

not  been  greater  than  with  bronchitis.  The  lesion  lias  oc- 
curred in  association  with  I>.  influenzae  and  pneumococci 
unassociated  with  oilier  microorganisms.  It  seems  prob- 
able that  the  severity  of  injury  to  the  bronchial  and  al- 
veolar walls  accompanied  by  recurring  bacterial  invasion 
or  by  continued  infection  with  B.  influenzae  and  one  or  sev- 
eral cocci,  is  the  factor  concerned  in  the  inhibition  of  reso- 
lution and  the  production  of  chronic  pneumonia.  II'  the 
disease  does  not  result  in  early  death,  chronic  pneumonia 
has  an  opportunity  to  manifest  itself. 

In  this  investigation  of  the  bacteriology  and  pathology 
of  influenza  and  its  complications,  certain  microorganisms 
have  been  found  so  frequently  that  it  is  desirable  to  discuss 
the  pathogenicity  of  each  and  to  define  the  character  of 
the  lesions  which  it  causes. 

Bacillus  Influenzae. — The  microorganism  has  been  con- 
stantly found  in  association  with  influenza  when  cultures 
and  animal  inoculations  have  been  made  from  various  parts 
of  the  respiratory  tract  within  from  one  to  five  days  after 
the  onset  of  the  disease  at  a  time  when  there  have  been 
acute  symptoms  of  the  disease. 

It  is  often  identified  with  difficulty  in  the  presence  of 
other  microorganisms  and  may  be  overlooked  when  a  single 
culture  is  made.  Repeated  cultures  from  the  throat  alone 
made  from  the  fourth  to  the  eighth  day  after  admission  to 
the  hospital,  at  a  time  when  temperature  had  fallen  to  nor- 
mal, have  demonstrated  the  presence  of  B.  influenza?  in 
30.5  per  cent,  whereas  the  incidence  of  the  microorganism 
in  similar  cultures  on  admission  had  been  63.4  per  cent. 
The  incidence  of  B.  influenzae  in  the  present  epidemic  of 
influenza  is  not  less  than  that  found  by  Pf eiffer  in  the  epi- 
demic which  he  studied  in  1892. 

Nevertheless  we  have  found  that  B.  influenza?  is  fre- 
quently an  inhabitant  of  the  mouth  and  throat  of  normal  in- 
dividuals. By  inoculation  of  mice  with  the  saliva  or 
sputum  of  76  patients  with  influenza,  the  microorganism 


370     PNEUMONIAS  AN'li   [NFECTIONS  OF  RESPIRATORS  TRACT 

has  been  found  in  80.3  per  cent;  by  inoculation  of  mice 
with  tlic  saliva  of  IS.")  normal  men  at  army  cantonments,  it 

was  found  in  41.6  per  cent;  by  inoculation  of  mice  with 
saliva  from  50  recruits  immediately  after  they  were  as- 
sembled from  isolated  farming  communities  where  only  a 
few  cases  of  influenza  had  occurred,  it  was  found  in  22  per 
cent.  Figures  for  the  same  groups  examined  by  a  single 
throat  culture  were  as  follows:  65.7  per  cent,  25.9  pel-  cent 
and  0  per  cent. 

Experiments  which  we  have  performed  on  monkeys  show 
that  inoculation  of  the  nasopharynx  with  B.  influenzae  ob- 
tained from  patients  with  influenza  is  followed  by  ill- 
defined  symptoms  associated  with  the  presence  of  B.  in- 
fluenzae within  tlie  throat.  After  from  two  to  eleven  days 
the  symptoms  and  the  microorganism  disappear.  Injection 
of  B.  influenzae  into  the  trachea  causes  bronchitis  and  the 
microorganism  may  be  recovered  from  the  inflamed  bronchi 
two  or  three  days  after  inoculation. 

The  constant  association  of  B.  influenzae  with  influenza 
suggests  that  it  is  the  cause  of  the  disease.  Its  widespread 
occurrence  in  the  throats  of  normal  individuals  does  not 
contradict  this  view,  since  pnoumoeocci  long  indistinguish- 
able from  those  which  usually  cause  lobar  pneumonia  are 
commonly  found  in  the  throats  of  healthy  men.  It  is  pos- 
sible that  B.  influenzae  is  a  secondary  invader,  entering  the 
respiratory  tract  when  susceptibility  is  increased  by  an  un- 
known virus  causing  influenza;  but  there  is  no  convincing 
evidence  in  favor  of  this  view.  It  is  desirable  to  determine 
if  microorganisms  having  the  characters  of  B.  influenzae 
found  with  influenza  differ  in  type  from  those  found  in  the 
throats  of  healthy  men  and  if  t lie  invasion  of  the  respiratory 
tract  by  B.  influenzae  is  followed  by  the  appearance  of  im- 
munity reactions  in  the  serum  of  the  patient.  Experiments 
on  monkeys  demonstrate  the  pathogenicity  of  the  micro- 
organism. 


SUMMATIY  OF  INVESTIGATION   AND  CONCLUSIONS  '■'>(  1 

The  relation  of  B.  influenzae  to  11k-  bronchitis  of  influenza 
indicates  that  it  lias  a  part  in  the  production  of  the  pul- 
monary sequela  of  influenza.  The  microorganism  has 
been  found  by  a  single  culture  from  the  bronchial  passages 

in  80  per  cent  of  instances  of  bronchitis  with  fatal  pneu- 
monia following  influenza  and  is  probably  constantly  pres- 
ent, usually  in  immense  number,  in  the  bronchial   mucus. 

It  is  obtained  from  the  pneumonic  lung  in  only  about  40 
per  cent  of  instances,  and  microscopic  examination  of  pre- 
pared tissue  shows  that  a  bacillus  with  the  morphology  of 
B.  influenza?  is  often  demonstrable  in  the  bronchial  pas- 
sages but  seldom  in  the  alveoli  of  the  lung.  The  microor- 
ganism is  well  adapted  to  multiply  under  conditions  present 
in  the  bronchi  but  doubtless  readily  disappears  from  the 
alveoli  which  are  the  site  of  an  inflammatory  reaction.  The 
microorganism  has  an  important  part  in  the  production  of 
the  associated  mucopurulent  and  hemorrhagic  inflammation 
of  the  bronchi,  but  it  is  rarely  if  ever  found  in  pure  cul- 
ture, being  associated  with  a  considerable  variety  of  pyo- 
genic cocci  and  occasionally  bacilli.  Infection  of  the  bron- 
chi with  B.  influenzae  in  immense  numbers  offers  an  ex- 
planation of  the  severity  of  the  inflammatory  process  within 
the  bronchi,  and  of  the  subsequent  dilatation  and  other 
chronic  changes  which  occur  in  them.  The  presence  of 
the  microorganism  and  the  accompanying  injury  to  the  cil- 
iated epithelium  and  mucous  glands  are  important  factors 
in  lowering  the  resistance  of  the  bronchial  passages  to 
secondary  bacterial  infection. 

We  have  obtained  no  evidence  that  B.  influenzae  alone 
is  capable  of  causing  pneumonia.  Its  occurrence  in  less 
than  half  of  all  pneumonic  lungs  is  explainable,  in  part  at 
least,  by  its  presence  in  the  terminal  bronchi  which  are  cut 
across  whenever  the  lung  is  punctured  for  culture.  B.  in- 
fluenza? alone  has  been  found  only  once  among  153  pneu- 
monic lungs  from  which  cultures  were  made,  and  in  this 
instance  (Autopsy  487)  S.  hemolyticus  present  in  the  blood 


372      PNEUMONIAS  AND   [NFECTIONS  OF  RESPIRATOR'S  TRACT 

of  the  heart,  pleural  cavity  and  bronchus  doubtless  had  a 
part  in  the  production  of  the  associated  pneumonia.  Pfeif- 
fer  maintained  thai  the  lesion  we  have  designated  hemor- 
rhagic peribronchiolar  consolidation  was  characteristic  of 
infection  with  his  microorganisms.  With  this  lesion  B. 
influenzae  lias  been  round  in  the  lungs  in  slightly  more  than 
half  of  our  autopsies  luit  never  alone,  pneumococci  being 
found  in  a  third,  hemolytic  streptococci  in  more  than  a  half 
and  staphylococci  in  a  fourth  of  the  lungs  examined. 

B.  influenza?  has  relatively  little  capacity  to  penetrate 
from  the  bronchi  into  the  hint;-  tissue  and  rarely  penetrates 
into  the  pleural  cavity  (once  with  Pneumococeus  III,  once 
with  S.  hemolyticus  and  once  in  pure  culture),  and  only 
once  has  it  been  found  in  the  blood  of  the  heart,  in  this 
instance  in  company  with  S.  hemolyticus.  Capacity  of  the 
microorganism  to  penetrate  from  the  bronchi  into  other 
tissues,  both  in  man  and  as  our  experiments  have  shown 
in  the  monkey,  is  increased  by  association  with  pyogenic 
cocci. 

Pneumococeus. — Lobar  pneumonia  following  influenza, 
like  lobar  pneumonia  in  civil  life  unassociated  with  in- 
fluenza, has  been  caused  by  pneumococci,  but  there  is  the 
notable  difference  that  the  pneumococci  usually  found  are 
those  types  which  are  commonly  present  in  the  mouths  of 
healthy  men,  namely,  Types  IV,  III  and  atypical  II  and 
not  the  so-called  fixed  types,  namely,  Types  I  and  II,  which 
represent  the  usual  cause  of  lobar  pneumonia  unassociated 
with  influenza.  It  appears  that  influenza  increases  suscep- 
tibility to  lobar  pneumonia,  so  that  it  is  frequently  caused 
by  microorganisms  which  under  other  conditions  are  less 
capable  of  producing-  this  lesion.  The  association  of  the 
pneumococci  usually  found  in  the  mouth  with  the  lobar 
pneumonia  of  influenza  does  not  exclude  the  possibility  that 
pneumococci  transmitted  from  one  individual  to  another, 
when  newly  recruited  troops  are  brought  together,  have 
an  Important  pari  in  the  production  of  pneumonia. 


SUMMARY  OF  INVESTIGATION  AND  CONCLUSIONS  373 

Bronchopneumonia  is  frequently  caused  by  pneumococci 

and  the  types  which  are  recovered  from  the  lung  and  Mood 
do  not  differ  from  those  found  with  lobar  pneumonia,  those 
usually  present  in  the  mouth  being  predominant,  but  the 
incidence  of  pneumococci  with  bronchopneumonia  has  been 
much  less  than  with  lobar  pneumonia.  Both  lobar  and 
bronchopneumonia  caused  by  pneumococci  have  undergone 
secondary  infection  with  hemolytic  streptococci  in  a  large 
proportion  of  instances  and  both  pneumococci  and  strep- 
tococci are  often  recovered  at  autopsy.  Nevertheless,  the 
bacterial  flora  of  the  bronchi  and  lungs  is  much  more  varied 
with  broncho  than  with  lobar  pneumonia,  and  it  is  evident 
that  microorganisms  other  than  pneumococci  are  capable 
of  causing  bronchopneumonia. 

In  instances  of  bronchopneumonia  associated  with  pneu- 
mococci, fibrin  has  been  abundant  in  the  alveolar  exudate. 

The  pneumococcus  exhibits  a  notable  tendency  to  pro- 
duce an  inflammatory  process  which  extends  through  the 
bronchial  walls  and  from  one  alveolus  through  the  alveolar 
walls  to  those  adjacent,  for  in  6  instances  in  which  the 
bronchi  were  surrounded  by  pneumonic  consolidation  rec- 
ognizable at  autopsy,  pneumococci  were  uniformly  the 
causative  agent,  Pneumococcus  Type  II,  otherwise  rarely 
found,  being  present  in  half  of  these  cases. 

Pneumonia  caused  by  one  type  of  pneumococcus  does 
not  necessarily  confer  immunity  from  other  types  of  pneu- 
mococci, and  with  somewhat  limited  opportunity  we  have 
observed  a  number  of  instances  in  which,  following  recov- 
ery from  pneumonia  caused  by  one  type  of  pneumococcus, 
a  second  attack  of  pneumonia,  usually  fatal,  has  been  as- 
sociated with  pneumococci  of  a  different  type.  This  re- 
curring pneumonia  in  a  considerable  proportion  of  the  rela- 
tively small  number  of  instances  observed  has  been  pro- 
duced by  Pneumococcus  Type  II  which  otherwise  has  been 
seldom  found  among  the  cases  which  we  have  studied.    The 


374      PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATORS  TRACT 

virulence  of  this  microorganism  doubtless  explains  its  abil- 
ity to  cause  recurrent  pneumonia. 

Streptococcus  Hemolyticus.-  -Secondary  infection  withS. 
hemolyticus  is  a  common  evenl  during  the  course  of  Lobar 
pneumonia  following  influenza.  It  is  noteworthy  thai  this 
streptococcus  infection  of  the  Lung  Lias  almost  invariably 
occurred  in  the  stage  of  red  hepatization,  whereas  with  gray 
hepatization,  when  the  alveoli  are  Tilled  with  polynuclear 
Leucocytes,  S.  hemolyticus  rarely  invades  the  hum'.  It  is 
possible  that  infection  with  S.  hemolyticus  tends  to  prolong 
the  stage  of  red  hepatization. 

The  most  significant  change  produced  in  the  pneumonic 
hum-  by  streptococci  is  necrosis.  When  after  death  with 
lobar  pneumonia  hemolytic  streptococci,  usually  associated 
with  pneumococci,  are  found  both  in  the  lungs  and  blood 
of  the  heart,  the  Lung  contains  patches  of  necrosis  recog- 
nized microscopically,  in  which  the  alveolar  walls  and  ex- 
uded cells  have  uniformly  lost  their  nuclei.  Microscopic 
examination  demonstrates  the  presence  of  chains  of  strep- 
tococci in  immense  number  in  these  necrotic  foci;  elsewhere 
chains  of  streptococci  occur  but  are  much  less  abundant. 
In  some  instances  streptococci  exhibit  a  tendency  to  enter 
Lymphatics  and  to  cause  acute  lymphangitis  with  lymphatic 
thrombosis  and  edema  of  the  adjacent  interstitial  tissue. 

Eemolytic  streptococci  have  been  more  frequently  found 
in  association  with  broncho-  than  with  lobar  pneumonia. 
In  24.5  per  cent  of  instances  of  lobar  pneumonia,  doubtless 
in  all  instances  caused  by  pneumococci,  hemolytic  strep- 
tococci have  invaded  the  lungs  and  in  12.6  per  cenl  of  in- 
stances have  found  their  way  into  the  blood  With  bron- 
chopneumonia hemolytic  streptococci  have  been  obtained 
from  the  lungs  in  29.8  per  cent  of  instances  and  from  the 
blood  of  the  heart  in  34.3  per  cent. 

With  Lobar  pneumonia  there  is  Little  doubt  that  pneu- 
mococcus  has  been  the  primary  cause  of  pneumonia,  but 
with  bronchopneumonia   pneumococci   have  been  less  fre- 


SUMMARY  OF  INVESTIGATION  AND  CONCLUSIONS  d70 

quently  found.  Tt  is  difficult  to  determine  how  often  hem- 
olytic streptococci  have  invaded  a  bronchopneumonia  lesion, 
caused  by  pneumococci  because  pneumococci  tend  to  disap- 
pear. In  numerous  instances  in  which  the  sputum  had  been 
studied  during  life,  it  was  evident  that  pneumonia  was  pri- 
marily referable  to  pneumococci,  and  hemolytic  streptococci 
made  their  appearance  in  the  sputum  late  in  the  disease  or 
were  first  recognized  at  autopsy. 

When  hemolytic  streptococci  occur  in  association  with 
bronchopneumonia,  foci  of  pulmonary  necrosis  similar  to 
those  found  under  the  same  conditions  with  lobar  pneu- 
monia have  been  repeatedly  found  by  microscopic  exam- 
ination. In  the  patches  of  necrosis,  cocci  in  chains  are 
much  more  abundant  than  in  the  tissue  elsewhere. 

In  some  instances  of  pneumonia,  caused  by  hemolytic 
streptococci,  opaque  gray  or  yellowish  gray  patches  of 
necrosis  occur  upon  a  background  of  flaccid  homogeneous 
consolidation  which  has  a  peculiar  cloudy,  gray  color. 
This  mottled  consolidation  may  implicate  an  entire  lower 
lobe  and  has  the  characteristic  features  neither  of  lobar 
nor  of  bronchopneumonia.  More  frequently  the  lesion  is 
less  widespread  and  necrosis  occurs  in  one  or  several  spots 
which  undergo  softening  so  that  finally  a  small  abscess 
cavity  may  be  formed ;  it  is  surrounded  by  pneumonic  con- 
solidation which  is  soft  and  has  the  cloudy  appearance  de- 
scribed above.  These  pulmonary  abscesses  are  almost  in- 
variably situated  below  the  pleural  surface;  the  adjacent 
pleural  cavity  is  infected  by  streptococci  and  there  is  puru- 
lent inflammation  of  the  pleura. 

Streptococcus  infection,  which  has  been  described,  doubt- 
less has  its  origin  in  the  bronchi,  for  in  favorable  sections 
it  is  not  infrequently  possible  to  demonstrate  that  necrosis 
extends  through  the  bronchial  walls  into  the  surrounding 
alveolar  tissue  and  is  followed  by  suppuration  with  abscess 
formation.     Localization  of  abscesses  below  the  pleura  is 


376      PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATORS   TRACT 

in  pari  at  least  referable  to  transmission  of  streptococci 
by  way  of  the  lymphatics. 

Streptococci  in  the  lung,  as  in  other  tissues,  often  invade 
lymphatics  and  produce  an  acute  inflammatory  reaction 
within  and  aboul  these  vessels.  The  peculiar  lesion  which 
may  be  designated  suppurative  interstitial  pneumonia  is 
a  suppurative  lymphangitis  associated  with  inflammation 
and  edema  of  the  interstitial  tissue  Lymphatics  invaded 
by  streptococci  are  the  site  of  acute  lymphangitis :  occlusion 
by  fibrinous  thrombi  occurs  and  finally  the  immensely  dis- 
tended lymphatics,  filled  with  purulent  fluid,  take  a  char- 
acteristic nodular  or  beaded  form  and  pus  (lows  from  them 
when  they  are  cut.  Streptococci  are  present  in  vast  num- 
bers. Suppurative  inflammation  may  extend  to  the  sur- 
rounding interstitial  tissue  which  is  distended  by  inflam- 
matory edema.  This  interstitial  suppurative  pneumonia 
extends  up  to  the  pleural  surface  and  empyema  is  almost 
invariably  associated  with  it.  The  lesion  is  seldom  seen 
in  the  absence  of  influenza. 

One  of  the  most  significant  characters  of  S.  hemolyticus 
is  its  ability  not  only  to  enter  the  bronchi  and  penetrate 
into  the  tissue  of  the  Inns;,  but  to  find  its  way  into  more 
distant  structures,  namely,  the  pleural  cavity,  pericardial 
sac  and  peritoneal  cavity  and  to  penetrate  into  the  blood. 
Among  121  examinations,  hemolytic  streptococci  were 
found  in  the  bronchi  in  47.!)  per  cent;  among  153  examina- 
tions of  the  lung-  it  was  present  in  approximately  the  same 
proportion,  namely,  50.3  per  cent;  among  218  examina- 
tions of  the  blood  it  was  found  in  39  per  cent.  In  4  of  5 
fatal  pneumonias  in  which  the  organism  has  penetrated  into 
the  bronchi  it  has  ultimately  found  its  way  into  the  blood. 

Nonhemolytic  Streptococci.  In  contrast  with  S.  hemo- 
lyticus nonhemolytic  types  have  rarely  been  encountered 
in  association  with  the  pneumonias  of  influenza.  S.  viri- 
dans  has  been  found  only  5  times  among  153  autopsies  in 
which  cultures  have  been  made  from  the  lung  and  has  been 


SUMMARY  OF  INVESTIGATION  AND  CONCLUSIONS  Oil 

invariably  associated  with  oilier  microorganisms.  In  no 
instances  have  nonhemolytic  streptococci  been  found  with 
empyema.  In  one  autopsy  with  lobular  bronchopneumonia 
S.  viridans  has  been  isolated  from  the  blood  of  the  heart 
and  in  this  instance  it  has  been  found  in  the  bronchus  and 
lung  as  well.  This  type  of  streptococcus  is  evidently  little 
adapted  to  invade  the  bronchi  and  produce  lesions  of  the 
lung-  and  adjacent  tissues. 

Staphylococci. — Staphylococci  have  been  very  frequently 
isolated  from  the  bronchi  in  association  with  the  pneu- 
monias of  influenza,  being  found  in  approximately  half  of 
our  autopsies.  Their  isolation  in  cultures  from  the  lung 
in  a  fourth  of  the  autopsies  examined  is  in  part  perhaps 
referable  to  their  presence  in  the  small  bronchi  cut  across 
when  the  lung  is  punctured  for  cultures.  S.  aureus  shows 
little  ability  to  invade  the  pleura,  being  found  in  associa- 
tion with  empyema  only  3  times;  in  these  autopsies  there 
has  been  opportunity  for  entrance  from  the  exterior 
through  thoracotomy  wounds  in  2  instances  and  from  a 
bronchus  in  free  communication  with  an  abscess  which  had 
ruptured  into  the  pleural  cavity  in  1  instance. 

Abscesses  of  the  lung  caused  by  staphylococci  have  been 
found  in  a  small  number  of  autopsies  and  have  exhibited 
characters  which  differ  from  those  ordinarily  seen  in  as- 
sociation with  S.  hemolyticus.  Small,  sharply  denned  ab- 
scesses are  grouped  about  terminal  bronchi,  so  that  they 
occur  in  one  or  several  isolated  clusters.  Microscopic  ex- 
amination demonstrates  that  these  abscesses  have  arisen 
by  destruction  of  the  bronchial  walls  and  extension  of  sup- 
puration into  the  surrounding  alveolar  tissue;  clumps  of 
staphylococci  are  found  in  sections  through  the  abscess, 
and  cultures  made  from  the  pus  within  the  abscess  cavity 
demonstrate  the  presence  of  S.  aureus  or  albus,  but  the 
microorganism  may  be  missed  if  the  culture  is  made  from 
the  adjacent  lung  tissue.  It  is  noteworthy  that  there  is 
little  tendency  for  the  staphylococcus  to  infect  the  pleura 


378      PNEUMONIAS  AND  [NFECTIONS  OF   RESPIRATOR'S  TRACT 

for  even  though  these  clusters  of  abscesses  have  been  situ- 
ated jusl  below  the  pleura,  there  lias  been  ao  associated  em- 
pyema. 

Staphylococci  have  scant  tendency  to  cuter  the  blood  and 
have  been  obtained  Prom  the  blood  of  the  heart  only  once,  in 
this  instance  with  hemolytic  streptococci. 

Pneumonia  of  Measles.  -Pneumonia  following  measles 
lias  been  responsible  for  a  considerable  pari  of  the  deaths 
occurring  in  the  United  States  Army  during  the  period  of 
the  war.  The  importance  of  measles  as  a  factor  in  the 
production  of  pneumonia  is  illustrated  by  the  history  of 
pneumonia  at  Camp  Funston  from  the  establishment  of 
the  cam])  in  September,  li)17,  until  September,  1918.  Pneu- 
monia following  measles  occurred  throughout  the  year; 
but  in  association  with  the  high  incidence  of  measles  dur- 
ing the  second  half  of  November  and  the  first  half  of  De- 
cember, 1917,  there  was  an  outbreak  of  related  pneumonia 
characterized  by  frequent  empyema  and  a  mortality  of  45.3 
per  cent. 

During  the  period  of  our  investigation  at  Camp  Funston 
there  were  11_!  cases  of  measles,  but  no  pneumonia  occurred 
among-  them.  At  Camp  Pike,  during  the  period  of  observa- 
tion, there  was  an  outbreak  of  measles  almost  coincident 
with  the  epidemic  of  influenza,  and  among  867  cases  pneu- 
monia occurred  in  56,  otitis  media  in  48,  and  mastoiditis  in 
23.  Pneumonia  following  measles  was  almost  coincident 
with  that  of  influenza,  and  it  is  not  improbable  that  the  epi- 
demic of  influenza  had  an  important  part  in  the  production 
of  pneumonia  in  individuals  suffering  with  measles. 

In  !>  of  56  instances  of  pneumonia  following  measles  at 
Camp  Pike,  S.  hemolyticus had  invaded  the  lung  and  caused 
pneumonia:  among  48  instances  of  otitis  media  following 
measles  a  very  large  proportion  were  caused  by  hemolytic 
streptococci,  and  l'l  of  23  instances  of  mastoiditis  were 
caused   by    the    same    microorganism.      No   complication 


SUMMARY  OF  INVESTIGATION   AND  CONCLUSIONS  379 

caused  by  S.  hemolyticus  occurred  among  '.'>7  patients  who 
carried  this  microorganism  when  admitted  to  the  hospital. 

A  special  study  has  been  made  to  determine  if  those  pa 
tients  with  measles  who  carry  S.  hemolyticus  in  their 
throats  are  especially  susceptible  to  complications  during 
the  course  of  measles.  The  low  incidence  of  streptococcus 
"carriers"  among  those  admitted  to  the  hospitals  with 
measles  was  noteworthy  both  at  Camp  Punston  (2. 07  per 
cent)  and  at  Camp  Pike  (4.2  per  cent).  Indeed,  it  was 
found  at  both  places  that  the  incidence  of  hemolytic  strep- 
tococci in  the  throats  of  normal  men  in  the  camp  was  higher 
(Camp  Funston  21.9  per  cent;  Camp  Pike  7.4  per  cent) 
than  that  in  the  throats  of  those  admitted  with  measles. 
While  in  the  hospital  there  was  a  gradual  increase  of  the 
incidence  of  S.  hemolyticus,  so  that  in  three  weeks  it  had 
risen  to  19  per  cent  at  Camp  Funston  and  to  26.2  per  cent 
at  Camp  Pike.  It  seems  not  improbable  that  hemolytic 
streptococci  disappear  from  the  throat  in  the  early  stages 
of  measles,  so  that  they  are  not  demonstrable  by  cultural 
methods.  During  the  course  of  the  disease  in  the  hospital 
ward  the  number  of  those  with  S.  hemolyticus  has  increased 
in  some  wards  with  great  rapidity,  infection  being  appar- 
ently transmitted  from  one  individual  to  those  adjacent. 
At  Camp  Funston  the  incidence  of  S.  hemolyticus  in  the 
throats  of  those  convalescent  with  measles  was  almost 
identical  with  that  among  normal  men  in  organizations  from 
which  the  patients  had  come,  but  at  Camp  Funston  the 
percentage  of  hemolytic  "carriers"  among  convalescents 
was  much  higher  than  that  obtained  among  normal  men 
in  the  camp. 

The  demonstration  of  S.  hemolyticus  in  the  throat  of  a 
patient  suffering  with  pneumonia  is  not  conclusive  }Droof 
that  the  lungs  have  been  invaded  by  this  microorganism. 
Pneumonia  in  indivduals  carrying  S.  hemolyticus  in  the 
throat  may  pursue  a  favorable  course  and  exhibit  no  evi- 
dence that  the  microorganism  has  found  its  way  into  the 


380      PNEUMONIAS  AND   [NFECTIONS  OF   KKSIMKATOUY  TRACT 

lung.     In  some  instances  hemolytic  streptococci  have  been 

round  in  the  bronchi  at  autopsy  yet  none  have  entered  the 
lung  or  blood  and  the  lung  exhibits  none  of  the  lesions  which 
are  referable  to  hemolytic  streptococci.  Nevertheless,  the 
occurrence  of  S.  hemolyticus  in  cultures  from  the  throat  of 
a  patient  with  pneumonia  suggests  the  probability  thai  he 
is  suffering  with  streptococcus  pneumonia. 

Pneumonia  following  measles  studied  in  18  autopsies 
upon  patients  who  died  during  or  shortly  after  the  epi- 
demic of  influenza,  exhibited  all  the  characters  exhibited  by 
the  pneumonias  of  influenza.  In  4  instances  there  was  typ- 
ical lobar  pneumonia;  bronchopneumonia  was  found  in  all 
but  3  instances,  being-  associated  with  lobar  pneumonia 
twice.  All  the  noteworthy  features  of  the  bronchopneu- 
monia of  influenza  have  been  reproduced  among-  these  in- 
stances of  pneumonia  with  measles;  there  is  severe  injury 
to  the  bronchi,  and  purulent  bronchitis  has  been  present  in 
13  instances ;  pneumonia  has  frequently  had  a  hemorrhagic 
character,  hemorrhagic  peribronchiolar  pneumonia  occur- 
ring in  5  instances ;  secondary  infection  of  the  pneumonic 
lungs  with  hemolytic  streptococci  has  been  common;  bron- 
chiectasis has  been  associated  with  bronchitis  (in  8  in- 
stances) when  purulent  bronchitis  has  persisted  several 
weeks;  and  unresolved  bronchopneumonia  has  been  more 
frequent  (6  instances  or  one-third  of  the  autopsies)  than 
with  influenza. 

The  bacteriology  of  pneumonia  following  measles  has 
been  the  same  as  that  of  influenzal  pneumonia.  B.  influ- 
enza? is  found  with  few  exceptions  in  the  bronchi  and  much 
less  frequently  in  the  pneumonic  lungs. 

Pneumococci  have  been  obtained  from  the  blood  or  lungs 
in  5  of  13  instances  of  lobar  or  bronchopneumonia  unac- 
companied by  suppuration;  when  suppuration  has  been  ab- 
sent no  hemolytic  streptococci  have  been  found.  Pneumo- 
cocci concerned  in  the  production  of  pneumonia  of  measles, 
as   with    influenzal    pneumonia,   have   been   types   usually 


SUMMARY  OF  INVESTIGATION  AND  CONCLUSIONS  38] 

found  in  the  mouth;  Pneumococcus  II  atypical   1ms  been 
found  6  times,  Type  IV  once,  Type  I  once. 

Hemolytic  streptococci  have  invaded  the  pneumonic  lung 
in  5  instances.  They  have  produced  subpleural  abscesses 
accompanied  by  empyema  in  2  instances.  Interstitial  sup- 
purative pneumonia,  a  lesion  repeatedly  found  in  conse- 
quence of  secondary  infection  with  S.  hemolyticus  follow- 
ing influenza  and  rarely  found  in  this  country,  at  least 
in  the  absence  of  an  epidemic  of  influenza,  has  occurred 
3  times  among  18  instances  of  pneumonia  following  measles. 

The  foregoing  observations  show  that  the  pneumonia  fol- 
lowing measles,  which  has  occurred  almost  coincidentally 
with  pneumonia  accompanying  epidemic  influenza  has  re- 
produced the  lesions  found  with  influenzal  pneumonia. 
The}''  indicate  that  influenza  attacking  patients  with  measles 
has  had  a  part  in  the  production  of  this  pneumonia. 

The  Transmission  of  Streptococcus  Pneumonia. — The  im- 
portance of  streptococcus  as  a  cause  of  pneumonia  follow- 
ing influenza  was  recognized  during  the  pandemic  of  1889- 
90.  Patients  suffering  with  pneumonia  following  influenza 
or  measles  are  susceptible  to  infection  by  S.  hemolyticus 
and  this  streptococcus  pneumonia  may  be  transmitted  from 
one  patient  to  another  throughout  a  ward  in  which  patients 
with  pneumonia  are  assembled.  There  is  no  evidence  that 
primary  pneumonia  caused  by  S.  hemolyticus  has  prevailed 
as  an  epidemic  in  the  army  or  elsewhere  in  the  absence  of 
preceding  infection  with  influenza  or  measles. 

Our  autopsies  demonstrate  that  at  least  half  of  all  deaths 
which  have  occurred  at  Camp  Pike  have  been  caused  by 
hemolytic  streptococci  which  have  invaded  the  lung  and 
entered  the  blood.  It  is  significant  that  this  mortality  had 
its  origin  in  the  first  half  of  the  epidemic  of  influenza  at  a 
time  when  the  military  and  medical  organization  of  the 
camp  was  confronted  with  an  unforseen  emergency  which 
overwhelmed  all  agencies  for  the  care  of  disease.  Curves 
prepared  by  referring  cases  of  pneumonia  in  which  an- 


382      PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATOR'S  TRACT 

topsy  demonstrated  the  nature  of  the  fatal  infection  back 
to  the  date  of  the  ousel  of  influenza,  demonstrate  thai  fatal 
streptococcus  pneumonia  was  frequently  acquired  during 
the  early  period  of  the  epidemic,  the  maximum  number  of 
cases  occurring  September  23  and  24  and  became  grad- 
ually less  common  as  a  sequela  of  the  influenza  which  be- 
gan at  a  Later  period.  Fatal  pneumococcus  pneumonia  had 
its  origin  with  increasing  frequency  at  a  later  period,  the 
maximum  incidence  following  influenza  which  had  its  onset 
September  29  and  30.  Overcrowding  of  influenza  patients 
in  infirmaries,  ambulances  and  hospital  had  an  important 
pari  in  the  dissemination  of  streptococcus  pneumonia 
among  influenza  patients  whose  disease  might  otherwise 
have  pursued  a  benign  course. 

The  most  important  factor  in  the  high  incidence  of  strep- 
tococcus pneumonia  has  been  the  spread  of  the  disease  in 
the  hospital  wards.  On  September  24  the  base  hospital 
contained  2,789  patients,  although  it  had  been  planned  to 
care  for  only  2,009.  With  the  progress  of  the  epidemic  the 
number  of  admissions  increased  very  rapidly,  so  that  on 
September  30  the  hospital  contained  8,587  patients  and  on 
October  5,  4,233.  After  September  24  the  milder  cases  of 
influenza  were  treated  in  barracks.  The  pressing  need  of 
diminishing  the  overcrowding  of  the  hospital  was  fully  rec- 
ognized and  adjacent  barracks  were  transformed  into  hos- 
pital wards;  between  October  3  and  6,  1,362  patients  were 
transferred  from  the  hospital  to  these  quarters. 

In  the  main  hospital,  during  the  period  of  overcrowding 
20  wards  for  patients  with  pneumonia  were  added  to  the  two 
which  already  existed.  These  hastily  organized  and  over- 
crowded wards  have  been  attacked  by  outbreaks  of  strep- 
tococcus pneumonia,  which  during  certain  periods  have 
been  fatal  to  more  than  two-thirds  of  those  who  have  been 
admitted  with  pneumonia,  whereas  in  the  two  loni»-  estab- 
lished wards  for  pneumonia  isolated  cases  of  streptococcus 
infection,  which  have  appeared,  have  failed  to  spread  to 


SUMMARY  OF  INVESTIGATION  AM)  COXCU  'SIOXS  383 

other  patients  and  pneumococcus  pneumonia  with  few  ex- 
ceptions has  been  found  in  those  who  have  died,  in  one 
newly  established  ward  07.5  per  cent  of  those  admitted 
within  a  period  of  three  days  have  died,  and  in  all  of  the 
23  autopsies  which  have  been  performed,  streptococcus 
pneumonia  has  been  found.  In  another  ward  50  per  cenl 
of  all  who  have  been  admitted  during  a  period  of  one  week 
have  died,  and  among  the  autopsies  performed  on  these 
individuals  pneumococcus  pneumonia  has  been  found  in 
6  and  streptococcus  pneumonia  in  14.  The  sputum  of  9 
patients  in  this  ward  has  been  examined  on  admission,  and 
pneumococci,  but  no  streptococci,  have  been  found.  All 
these  patients  have  died,  and  infection  with  S.  hemolyticus 
has  been  found  at  autopsy  in  7. 

Transmission  of  Pneumococcus  Pneumonia. — Our  study 
of  secondary  ward  infection  has  not  only  shown  that  pa- 
tients with  pneumococcus  pneumonia  following  influenza 
are  susceptible  to  infection  by  S.  hemolyticus,  but  that 
patients  suffering  with  pneumonia  caused  by  one  type  of 
pneumococcus  may  be  infected  with  another  type  during 
the  course  of  the  disease  or  after  convalescence  has  begun, 
the  second  infection  being  acquired  from  patients  in  ad- 
jacent beds.  Pneumonia  caused  by  Type  IV  has  ended  in 
crisis  and  has  been  followed  by  a  period  of  normal  tem- 
perature; recurrent  pneumonia  has  been  fatal  and  Pneu- 
mococcus Type  II  has  been  found  in  the  organs  at  autopsy. 
Pneumonia  caused  by  Type  I  has  been  followed  by  recur- 
rent pneumonia  caused  by  Pneumococcus  II  atypical  ac- 
quired from  a  patient  in  the  next  bed.  These  secondary 
pneumococcus  infections  acquired  within  the  hospital  are 
apparently  not  uncommon. 

Prevention  of  the  Transmission  of  Pneumonia. — The  es- 
sential factor  in  the  management  of  influenza  and  rmeu- 
monia  is  such  isolation  of  each  patient  that  microorganisms 
cannot  be  transmitted  from  one  to  another  or  from  attend- 
ants or  others  to  patients.     This  condition  may  be  fulfilled 


..S4      PNEUMONIAS  AND  [NFECTIONS  OF   RESPIRATORS  TRACT 

by  the  separation  of  patients  in  rooms  or  isolated  compart- 
ments especially  constructed  for  the  treatment  of  pneu- 
monia and  by  the  employmenl  of  all  possible  means  to  pre- 
vent the  transmission  of  infection  from  one  patient  to  an- 
other by  physicians,  nurses  and  orderlies.  It  is  desirable 
to  examine  attendants  to  determine  it'  they  carry  hemolytic 
streptococci  in  their  months  and  to  exclude  those  who  are 
found  to  be  "carriers." 

Inllnenza  is  a  self-limited  disease  which,  in  the  absence 
of  complications  implicating  the  lower  respiratory  tract, 
is  of  relatively  mild  character.  When  death  occurs  as  the 
result  of  influenza  it  is  with  very  rare,  if  any,  exceptions 
referable  to  pneumonia;  we  have  invariably  found  pneu- 
monia in  those  who  have  died  in  consequence  of  influenza. 
The  individual  attacked  by  influenza  may  carry  within  his 
upper  respiratory  passages  pneumococci  or  hemolytic 
streptococci  capable  of  invading  the  bronchi  and  causing 
pneumonia,  but  in  most  instances  the  microorganism  which 
produces  serious  pulmonary  complications  is  derived  from 
others  with  whom  the  influenza  patient  has  come  into  con- 
tact. The  greatest  source  of  danger  to  one  with  influenza 
is  contact  with  patients  who  have  acquired  pneumonia,  and 
this  danger  is  immensely  increased  when  infection  with  S. 
hemolyticus  makes  its  appearance  among  pneumonic  pa- 
tients. Hospital  epidemics  of  streptococcus  pneumonia 
will  be  prevented  when  the  disease  is  dreaded  as  much  as 
puerperal  fever  or  the  hospital  gangrene  of  former  years, 
and  widespread  knowledge  of  the  suppurative  pneumonias 
of  influenza  will  bring  a  clear  recognition  of  the  fatal  char- 
acter of  streptococcus  infection  in  patients  suffering  with 
pneumococcus  pneumonia. 

Overcrowding  of  barracks  has  been  an  important  fac- 
tor in  the  propagation  of  acute  respiratory  disease  and 
in  the  transformation  of  otherwise  trivial  inllnenza  into 
fatal  pneumonia.  Crowded  troop  trains  have  doubtless 
had   a  part  in  disseminating  infection  among  newly  as- 


SUMMARY  OF  INVESTIGATION  AND  CONCLUSIONS  385 

sembled  recruits.  Should  these  dangers  he  recognized  they 
may  be  avoided  by  appropriate  measures  which  will  pro- 
mote rather  than  retard  those  military  aims  which  must  be 
placed  foremost  in  time  of  Avar.  It  may  be  possible  by  ade- 
quate expenditure  to  avoid  the  death  of  thousands  of  re- 
cruits within  one  month  of  their  entrance  into  military 
service. 

A  second  factor  in  the  increase  of  death  rate  from  pneu- 
monia is  the  overcrowding  and  confusion  of  hospital  facil- 
ities in  Uie  presence  of  an  epidemic  disease.  When  troops 
are  maintained  in  camps  precautions  should  be  taken  to  pro- 
vide effective  safeguards  against  the  overcrowding  of  the 
base  hospital. 

Isolation  of  each  patient  with  pneumonia  is  the  most  ef- 
fective way  of  protecting  him  from  infection  and  of  pre- 
venting him  from  becoming  a  possible  source  of  danger  to 
others.  The  effectiveness  of  this  isolation  will  depend  upon 
the  separation  of  patients  by  some  means  more  effective 
than  the  cubicles  composed  of  sheets  heretofore  employed, 
upon  an  aseptic  technic  sufficiently  rigid  to  prevent  the 
transfer  of  pyogenic  infection  to  pneumonia  patients,  and 
upon  the  exclusion  from  the  ward  of  those  who  harbor  S. 
hemolyticus. 

Even  should  each  patient  be  completely  isolated  from 
his  neighbors,  no  effort  should  be  neglected  to  determine, 
as  far  as  possible,  the  nature  of  the  infection  with  which 
he  suffers.  In  the  presence  of  an  overwhelming  epidemic 
such  as  that  which  attacked  our  army  camps,  the  bacter- 
iologic  work  which  is  required  may  be  far  beyond  the  facil- 
ities which  are  available  and  in  many  instances  it  may  be 
wholly  impossible.  Nevertheless  effective  control  of  strep- 
tococcus pneumonia  will  depend  upon  its  recognition  as 
soon  as  it  appears,  and  bacteriologic  examination  of  the 
sputum  offers  the  readiest  means  for  its  identification. 
The  routine  performance  of  autopsies  will  furnish  an  index 
of  the  success  of  the  measures  in  force,  and  the  discovery 


386      PNEUMONIAS  A  N  I '    INFECTIONS  OF   RESPIRATOR!    TRACT 

of  suppurative  pneumonia  will  suggest  the  presence  of  im- 
minenl  danger. 

However  perfecl  the  organization  of  pneumonia  wards 
and  however  accurate  the  aseptic  technic  in  force,  it  is 
desirable  to  separate  as  far  as  possible  those  infected  with 
streptococcus  from  those  who  arc  free  from  this  infection, 
so  that  the  accuracy  of  the  technic  in  force  may  not  be  put 
to  too  severe  a  test.  When  streptococcus  pneumonia  has 
appeared  in  a  ward  it  should  he  closed  to  further  admissions. 

These  who  arc  concerned  in  the  planning  and  construc- 
tion of  military  and  other  similar  hospitals  iniejit  well  ,<>ive 
special  attention  to  the  possibility  of  epidemics  such  as 
those  which  we  have  experienced,  and  special  provision 
might  he  made  to  avoid  overcrowding  in  the  presence  of  a 
demand  far  in  excess  of  the  routine  need  for  hospital  facil- 
ities. In  the  construction  of  these  hospitals  appropriate 
provision  should  be  made  for  the  care  of  patients  with 
pneumonia.  Medical  officers  should  receive  detailed  in- 
struction in  the  organization  and  conduct  of  wards  designed 
for  the  treatment  of  pneumonia. 


APPENDIX 

EXPERIMENTAL     INOCULATION     OF     MONK  EYS 
WITH  BACILLUS  INFLUENZAE  AND  MICRO- 
ORGANISMS   ISOLATED    FROM    THE 
PNEUMONIAS     OF    INFLUENZA 

Eugene  L.  Opie,  M.D. ;  Allen  W.  Freeman,  M.D. ;  Francis 

Gr.  Blake,  M.D. ;  James  C.  Small,  M.D. ;  and 

Thomas  M.  Rivers,  M.D. 

Experiments  were  undertaken  at  Camp  Pike  in  Decem- 
ber, 1918,  to  determine  whether  bacteria  freshly  isolated 
from  patients  suffering  with  influenza  and  pneumonia  dur- 
ing the  outbreak  of  influenza  and  its  associated  pneumo- 
nias were  capable  of  producing  similar  diseases  when  in- 
troduced into  the  respiratory  passages  of  monkeys.  The 
number  of  animals  available  for  the  study  was  limited. 
The  attempt  was  made  (a)  to  determine  if  B.  influenzae 
produces  in  monkeys  a  disease  comparable  to  influenza  of 
human  beings,  and  (b)  to  determine  so  far  as  possible, 
with  the  limited  opportunity,  the  character  of  the  lesions 
produced  by  combinations  of  pneumococcus  or  S.  hemo- 
lyticus  with  B.  influenzae  and  to  compare  these  lesions  with 
lesions  produced  by  pneumococcus  or  by  hemolytic  strep- 
tococcus alone. 

Pfeiffer1  found  monkeys  alone  susceptible  to  invasion 
by  B.  influenzae  and  obtained  no  evidence  of  multiplication 
of  the  microorganism  within  the  body  of  any  other  animal. 
A  suspension  containing  mucus  from  the  sputum  of  a  pa- 
tient with  influenza  was  injected  into  a  monkey.  There  was 
elevation  of  temperature  and  the  animal  died  after  seven 
days.  Lobular  patches  of  atelectasis  occurred  along  the 
sharp    edges    of    the    lungs    and    the    adjacent    bronchial 


iPfeiffer:     Ztschr.  f.    Hyg.,    1S93,   xiii,   357. 

387 


388      PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATOR!    TRACT 

branches  contained  mucus.  Cultures  on  agar  from  tluv 
bronchi  remained  sterile.  Microscopic  examination  showed 
the  presence  of  bacilli  resembling  !>.  Influenzae.     Death  was 

caused,  the  author  states,  by  an  abscess  at  the  site  of  in- 
oculation and  aol  by  the  process  in  the  hums.  Three  mon- 
keys received  each  0.5  c.c.  of  bouillon  containing  a  blood 
agar  culture  injected  into  the  hum'  through  the  chest  wall. 
There  Avas  elevation  of  temperature  lasting  Prom  three  to 
five  days  with  return  to  normal  every  morning.  There 
was  cough  but  little  evidence  of  illness.  B.  influenzae  was 
introduced  by  a  platinum  loop  into  the  nose  of  a  monkey. 
Febrile  reaction  is  recorded  Lasting  four  or  live  days. 
Pfeiffer  found  that  guinea  pigs  and  mice  were  resistant  to 
the  microorganism.  Large  doses  injected  intravenously 
caused  in  rabbits  intoxication  with  dyspnea  and  evidence 
of  profound  muscular  weakness. 

Kamen2  used  a  culture  of  B.  influenzae  which  was  nonpath- 
ogenic tor  mice,  but  when  it  was  inoculated  into  the  peri- 
toneal cavity  with  streptococcus  both  influenza  bacilli  and 
streptococci  appeared  in  the  blood.  Jacobson3  found  that 
B.  influenza?  appeared  in  the  blood  and  viscera  of  mice 
killed  by  intraperitoneal  inoculation  of  B.  influenzae  mixed 
with  cultures  of  streptococcus  either  living  or  killed  by 
heat.  B.  influenza?  which  had  successively  passed  through 
mice,  simultaneously  inoculated  with  killed  streptococci, 
acquired  such  virulence  that  it  was  capable  of  producing 
septicemia  when  inoculated  alone. 

Richie4  introduced  by  lumbar  puncture  a  suspension  of 
two  blood  agar  cultures  of  B.  influenzae  obtained  from  the 
meninges  of  a  patient  with  influenzal  meningitis  into  the 
subdural  space  of  a  rhesus  monkey.  Death  occurred  in 
eighteen  hours  and  there  was  beginning  meningitis.  B.  in- 
fluenzae was  present  in  the  exudate  in  abundance. 


-Kamen,   L  :     Centralbl.    f.    Bakteriol.,    1901,   xxix,    Erste   A1>t.  339. 
'Jacobson,  G.:     Arch,  de  med.  exper.  et  d'anat.  path.,  1901,  xiii,  425. 
4Ricbie,  J.:     Journal   Path,  and   Bacterid.,    1910,  xiv,   615. 


APPENDIX  oSfJ 

In  two  species  of  monkeys  Wollstein5  produced  fatal 
meningitis  by  injecting  suspensions  of  l>.  influenza'  into  the 
subdural  space  by  lumbar  puncture. 

During  the  course  of  our  investigation  of  pneumonia  and 
influenza,  sputum  of  approximately  400  normal  individuals 
or  patients  with  influenza  was  injected  into  the  peritoneal 
cavity  of  mice.  B.  influenzae  was  found  in  approximately 
150  instances.  In  only  4  instances  was  B.  influenzae  found 
in  pure  culture  in  the  blood ;  in  all  other  mice  in  which  B. 
influenzas  appeared  in  the  blood  it  accompanied  pneunio- 
coccus  or  S.  hemolyticus. 

Before  experiments  were  performed  cultures  were  made 
from  the  throats  of  all  monkeys  in  order  to  exclude  the 
presence  of  B.  influenza?.  Blood  agar  plates  inoculated  with 
a  swab  applied  to  the  nasopharynx  failed  to  show  in  any 
instance  B.  influenza?,  pneumococci,  or  hemolytic  strep- 
tococci. Streptococci  causing  green  discoloration  of  blood 
agar  were  usually  found. 

Inoculation  of  the  Nose  and  Pharynx  with  B.  Influenzae. — 
B.  influenzas  was  introduced  into  the  nose  and  pharynx  of 
two  healthy  monkeys.  An  actively  growing  culture  of  the 
microorganism  made  on  alkaline  blood  agar  and  sixteen 
hours  old  was  used.  The  culture  was  the  first  subculture 
from  a  growth  obtained  from  the  nose  and  throat  of  a 
patient  with  influenza.  A  cotton  swab  moistened  with 
broth  was  applied  to  the  surface  of  the  culture.  It  was 
introduced  into  the  nostrils  and  smeared  over  the  pharynx 
of  the  animals.  A  swab  moistened  with  sterile  broth  was 
applied  to  the  nose  and  pharynx  of  a  third  monkey  as  a 
control;  cultures  from  this  animal  kept  in  a  cage  removed 
from  those  inoculated  failed  to  show  B.  influenza?. 

Experiment  1 
November  21,  1918. — Small  female  monkey;  throat  culture:  negative.     No- 
vember 23. — 10:20  A.M. — White  blood  corpuscles,   16,700;   polynuclear  leuco- 
cytes, 68  per  cent;  small  lymphocytes,  17.5  per  cent;  large  lymphocytes,  8  per 


5Wollstein.  M.:     Am.  Jour.  Dis.  Child.,   1911,  i,  42. 


390      PNEUMONIAS  AND   INFECTIONS  01   RESPIRATOR'S  TRACT 

(••■nt:  large  mononuclears,  I  pex  centj  eosinopbiles,  2.5  per  cent;  basinophiles, 
0.5  per  cent.  10:30  A.M.— Mucous  membranes  of  nose  and  throat  were  inoc- 
ulated with  B.  influenzae  as  described  above.  November  25.-  The  animal  ap- 
pears si.k  and  is  huddled  Ln  back  of  its  cage;  the  nose  is  running.  White  blood 
corpuscles,  L3,500;  polynuclear  leucocytes,  II  per  cent :  small  lymphocytes,  30 
per  cenl ;  large  lymphocytes,  22  per  cent  :  large  mononuclears,  3  per  eenl ;  eosin- 
opliiles,  1  per  cent.  3:40  P.M. — Free  epistaxis  occurred  after  culturing  of  nose; 
the  swab  was  discolored  with  old  brownish  blood  indicating  previous  epistaxis. 
Nose  culture:  B.  influenzae  present  in  abundance;  Gram-positive  cocci  present. 
Throat  culture:  negative  for  B.  influenzae.  November  28.— Monkey  is  more 
active  and  appears  to  be  fairly  well.  Nose  and  throal  cultures:  negative  for 
B.  influenzae.     December  4.— Monkey  is  apparently  well. 

Experiment  2 
November  21,  1918. — Small  male  monkey.  Throat  culture:  negative.  No- 
vember 23. — 10:10  A.M. — White  blood  corpuscles,  10,900;  polynuclear  leuco- 
cytes, .31'  per  cent:  small  lymphocytes,  is  per  cent;  largo  lymphocytes,  25  per 
cent;  large  mononuclears,  I!  per  cent;  eosinophiles,  2  per  cent.  10:15  A.M. — 
Mucous  membranes  of  nose  and  throat  wen'  inoculated  by  means  of  moist 
swab  with  4  strains  of  B.  influenzal  recently  isolated  from  acute  cases  of  in- 
fluenza. November  24. — Monkey  is  quiet  and  takes  no  interest  in  surroundings. 
November  25. — Animal  appears  sick  and  remains  huddled  at  back  of  its  cage. 
Nose  culture:  B.  influenzae  present.  Throat  culture:  B.  influenzal  present. 
Swab  applied  to  nose  is  stained  brown  with  old  blood  indicating  previous 
epistaxis.  November  2G. — Animal  is  still  sick;  nose  is  running.  White  blood 
corpuscles,  14,400;  polynuclear  leucocytes,  61  per  cent;  small  lymphocytes,  23 
per  cent;  large  lymphocytes,  15  per  cent;  large  mononuclears,  1  per  cent.  No- 
vember 27. — White  blood  corpuscles,  11,300.  November  28. — Nose  culture: 
negative  for  B.  influenza?.  Throat  culture:  B.  influenzal  present.  November 
29. — Animal  is  active,  but  still  appears  sick.  White  blood  corpuscles,  19,300. 
December  4. — Monkey  appears  well.     Throat  culture:   B.  influenza1  present. 

These  animals  were  sick  two  and  six  days  following  in- 
oculation. There  was  discharge  from  the  nose.  In  both  in- 
stances there  was  epistaxis.  The  temperature  of  the  ani- 
mals was  subject  to  such  wide  variation  in  relation  to  ex- 
ternal temperature  that  it  could  not  be  used  as  an  index  of 
the  progress  of  the  disease.  There  was  no  leucocytosis,  but 
in  one  animal  there  was  some  increase  in  the  numbers  of 
leucocytes  during  recovery.  In  one  animal  B.  influenzae 
present  in  the  nose  after  two  days  was  absent  after  four 
days.  In  the  other  animal  the  organism  was  repeatedly 
found  in  the  nose  and  throat  and  was  still  present  in  the 
throat  eleven  days  after  inoculation.    The  two  animals  suf- 


APPENDIX  .j  Jl 

fered  with  a  self-limited  disease  resembling  many  cases  of 
influenza. 

Introduction  of  Bacillus  Influenzae  into  the  Trachea. — In 
the  attempt  to  reproduce  the  bronchitis  which  occurs  in  a 
considerable  proportion  of  all  cases  of  influenza  and  is  al- 
most invariably  associated  with  B.  influenzae,  this  organism 
was  introduced  into  the  trachea  of  monkeys.  In  Experi- 
ment 3  a  suspension  containing  young  cultures  of  freshly 
isolated  B.  influenzas  was  introduced  into  the  trachea  by  a 
silver  catheter  passed  through  the  glottis  and  larynx  into 
the  trachea. 

Young  cultures  of  B.  influenzas,  subcultured  only  once 
after  isolation  from  early  cases  of  influenza,  were  used.  The 
microorganism  was  recovered  in  abundance  by  throat  swab 
two  days  later  and  again  from  the  bronchus  at  autopsy 
three  days  after  inoculation.  Tuberculosis  of  mesenteric 
lymph  nodes,  of  intestine  and  of  liver  and  several  small 
tuberculous  nodules  in  the  lung  were  found  at  autopsy.  A 
secondary  invasion  of  the  lung  by  staphylococci  had  oc- 
curred. There  was  bronchitis  with  an  inflammatory  infil- 
tration of  the  subepithelial  tissue  of  the  bronchi  by  lym- 
phoid and  plasma  cells.  Bronchopneumonia  was  present, 
and  the  bronchi  and  many  of  the  alveoli  contained  blood. 
These  changes  do  not  differ  essentially  from  the  changes 
found  in  many  instances  of  pneumonia  following  influenza. 

In  three  instances  cultures  of  B.  influenzas  were  injected 
into  the  trachea  by  means  of  a  hypodermic  syringe. 

In  one  of  these  experiments  (Experiment  4)  intratra- 
cheal injection  of  2  c.c.  salt  solution  suspension  of  B.  in- 
fluenzas (isolated  at  autopsy  from  bronchus  of  the  monkey 
used  in  Experiment  3),  representing  growth  on  iy2  blood 
agar  plates,  was  made  with  a  needle  inserted  into  trachea 
just  above  the  suprasternal  notch.  On  the  following  day  a 
throat  culture  contained  B.  influenzas  in  abundance.  Three 
days  after  inoculation  the  monkey  appeared  to  be  very  sick 
and    there    was    profuse    nasal    discharge.      The    animal 


392      PNEUMONIAS  AND   [NFECTIONS  OF   RESPIRATOR'S  TRACT 

coughed  and  sibilant  rales  were  beard  over  the  chest. 
There  was  no  Leucocytosis.     A  throat   culture  contained 

B.  influenzas.  Four  days  after  inoculation  the  monkey  was 
still  sick  and  weak,  luit  appeared  much  improved  and  was 
killed.  The  trachea  and  Large  bronchi  contained  thick  vis- 
cid mucus.  In  the  middle  Lobe  of  the  righl  Lung  was  a  patch 
of  grayish  red,  airless  tissue,  firmer  than  the  lung  substance 
elsewhere.  Cultures  from  the  trachea,  bronchus  and  lung 
contained  a  variety  of  microorganisms,  but  B.  influenzae  was 
not  recovered. 

In  two  additional  experiments  (Experiments  (>  and  7) 
cultures  of  B.  influenzae  forty-eight  hours  old  were  injected 
into  the  trachea  of  monkeys.  The  microorganism  was  re- 
covered in  cultures  made  Prom  the  pharynx  two  days  later. 
These  animals  were  only  slightly  sick. 

Introduction  of  B.  Influenzae  and  S.  Hemolyticus  into  the 
Trachea. — In  view  of  the  frequent  association  of  B.  influen- 
zae and  S.  hemolyticus  in  the  sputum  of  patients  with  strep- 
tococcus pneumonia  following  influenza  and  in  the  bronchi 
and  lungs  of  those  who  have  died  with  this  disease,  the  two 
microorganisms  were  injected  simultaneously  into  the  tra- 
chea of  monkeys. 

B.  influenzae  and  8.  hemolyticus  in  Experiment  7  pro- 
duced bronchitis  and  bronchopneumonia.  There  was  acute 
inflammation  of  the  interstitial  tissue  of  the  lung,  and  acute 
lymphangitis  with  numerous  polynuclear  leucocytes  within 
the  lumen  of  the  lymphatics  was  present.  B.  influenzae  and 
S.  hemolyticus  were  present  in  the  trachea  at  autopsy  four 
days  after  inoculation.  It  is  probable  that  part  of  the  in- 
jected culture  entered  the  tissue  outside  the  trachea,  for  an 
abscess  was  formed  in  this  situation.  It  is  noteworthy  that 
acute  pericarditis  occurred  and  both  S.  hemolyticus  and  B. 
influenzae  were  found  in  the  pericardial  exudate.  B.  influ- 
enzae not  infrequently  exhibits  this  tendency  to  penetrate  in 
association  with  other  bacteria  localities  which  it  does  not 
invade  independently. 


APPENDIX  393 

In  a  second  experiment  (Experiment  8)  in  which  B.  influ- 
enzae and  S.  hemolyticus  wore  injected  into  the  trachea, 
both  microorganisms  were  recovered  from  the  throat  on 
the  day  following  inoculation;  on  the  fifth  day  S.  hemo- 
lyticus  alone  was  recovered  and  on  the  sixth  day  a  throat 
culture  was  negative  both  for  S.  hemolyticus  and  B.  influ- 
enzae 

Introduction  of  B.  influenzae  and  of  Pneumococcus  or  of 
Pneumococcus  Alone  into  the  Trachea. — In  two  experi- 
ments B.  influenzae  and  Pneumococcus  Type  III  were  simul- 
taneously injected  into  the  trachea. 

In  Experiment  9  a  large  male  monkey  was  used  and  intra- 
tracheal injection  made  with  syringe  and  needle  of  5  c.c. 
salt  solution  suspension  of  Pneumococcus  Type  III  and  B. 
influenzae  (growth. on  5  blood  agar  plates  of  mixed  cultures 
of  Pneumococcus  III  and  B.  influenzae).  On  the  following 
clay  the  animal  was  very  sick,  lying  on  the  floor  of  its  cage, 
and  was  dead  two  days  after  inoculation. 

The  dosage  of  bacteria  in  this  exrjeriment  was  large.  The 
lesions  in  gross  appearance  and  microscopically  resembled 
those  seen  in  many  instances  of  pneumonia  following  influ- 
enza. In  the  trachea  there  was  loss  of  ciliated  epithelium, 
congestion  of  the  subepithelial  tissue,  hemorrhage  and  infil- 
tration with  plasma  cells.  The  lungs  were  consolidated  and 
red  and  there  were  hemorrhage  and  edema.  B.  influenzae, 
as  in  human  cases,  was  abundant  in  the  bronchi,  less  abun- 
dant in  the  consolidated  lung,  being  present  though  scant 
in  the  left  lung,  and  absent  in  cultures  from  the  right.  B. 
influenzae  as  in  Experiment  8  with  streietoeoeeus  had  en- 
tered the  left  pericardial  cavity  in  company  in  this  experi- 
ment with  Pneumococcus  III. 

In  Experiment  10  a  very  large  monkey  received  by  intra- 
tracheal injection,  made  with  syringe  and  needle,  5  c.c.  salt 
solution  suspension  of  Pneumococcus  III  and  3  strains  of 
B.  influenzae,   (2  recently  isolated  from  cases  of  influenza 


394     PNEUMONIAS  AXD  INFECTIONS  01   RESPIRATORS  TRACT 

and  1  from  autopsy  in  a  case  of  postinfluenzal  pneumonia). 
The  animal  3ied  twenty-four  hours  later. 

This  simultaneous  introduction  of  l>.  influenzae  and  Pneu- 
mococcus  III  in  large  quantity  lias  produced  rapidly  fatal 
pneumonia  with  lobar  distribution.  Eepatization  was 
homogeneous  and  rod,  and  outside  the  consolidated  parts 
of  the  lung  there  was  hemorrhage  and  edema.  The  lesion 
resembled  thai  round  when  death  lias  occurred  within  a  few 
days  after  the  onset  of  pneumonia  following  Influenza,  but 
had  no  distinctive  characters  establishing  its  relation  to 
pneumonia  following  influenzae. 

In  Experiment  11  Pneumococcus  III  alone  in  small 
amount  was  introduced  into  the  trachea  of  a  small  monkey. 
The  animal  was  very  sick,  but  its  condition  improved  and 
recovery  seemed  probable.  The  animal  was  killed  seven 
days  after  inoculation,  and  typical  lobar  pneumonia  with 
gray  hepatization  was  found  at  autopsy. 

Experiment  11 

November  20,  1918. — Small  monkey;  throat  culture:  negative  for  B.  influ- 
enzae, pneumococcus  and  S.  hemolytieus.  November  28  and  December  f>. — 
Nose  and  throat  cultures  again  negative  for  B.  influenzae.  December  0. — 
4  ::!ii  P.M. —  Intratracheal  injection  with  syringe  and  needle  of  0.33  c.c.  of  an 
eighteen  hour  broth  culture  of  Pneumococcus  Type  III.  December  10. — The 
animal  is  sick,  huddled  up  in  his  cage  with  head  down;  there  is  rapid  respi- 
ration with  expiratory  grunt  ami  the  mucous  membranes  are  moderately  cya- 
notic. There  is  frequent  cough.  Throat  culture:  Pneumococcus  111  presenl 
in  abundance.  December  15. — The  animal  appears  to  be  better.  Respirations 
are  still  rapid  but  less  labored.  December  16. — The  animal  is  improving  but 
very  weak  and  emaciated. 

Autopsy. — The  pleural  cavities  contain  no  Quid.  On  the  right  side  arc  sev- 
eral strands  (if  fibrin.  The  right  lower  lobe  with  the  exception  of  a  small 
patch  at  the  summit  and  the  lower  part  of  the  middle  lube  are  voluminous, 
have  a  dull  gray  surface  covered  by  a  scant  layer  of  fibrin  and  are  firmly  con- 
solidated. On  section  the  consolidated  tissue  has  a  gray  color  and  is  con- 
spicuously granular,  the  granulation  resembling,  on  a  slightly  smaller  scale, 
that  seen  in  human  lobar  pneumonia.  The  bronchi  contain  a  small  amount  of 
viscid  fluid. 

Bacteriology. — Direct  smears  from  the  trachea  and  the  lower  lobe  of  the 
left  lung  contain  Gram-positive  diplocoeci.  Cultures  from  the  trachea  and 
from  the  blood  of  the  heart  contain  Pneumococcus  lib  Cultures  from  the 
left  lower  lobe,  from   the  liver  and    from    the   spleen    remain    sterile. 


APPENDIX 


395 


Microscopical  Examination. — There  is  abundant  infiltration  of  the  subepi 
thclial  tissue  of  the  trachea  with  plasma  cells.  Superficial  ciliated  epithelium 
is  in  places  lost.  At  one  point  is  a  small  focus  of  hemorrhage.  Alveoli  in  the 
consolidated  part  of  the  lungs  contain  polynuelear  leucocytes  and  fibrin  and 
exhibit  the  appearance  seen  in   Lobar  pneumonia  in  man. 

In  Experiment  12  B.  influenzae  was  injected  into  the  tra- 
chea and  two  days  later  identified  in  a  culture  made  i'rom 


Fig.  33. — Experimental  lobar  pneumonia  in  the  stage  of  gray  hepatization  produced 
by  injection  of  Pneumococcus  III  into  the  trachea  of  a  monkey  (Experiment  11).  The 
alveoli  are  uniform!}'  filled   with   plugs   of  fibrinous   exudate. 

the  pharynx ;  four  days  after  inoculation  Pneumococcus  IV 
was  injected  into  the  trachea.  The  animal  was  killed  seven 
days  after  the  first  inoculation,  and  three  days  after  inocu- 
lation with  pneumococcus.  The  lower  half  of  the  upper 
lobe  of  the  right  lung  and  the  greater  part  of  the  lower  and 


396     PNEUMONIAS  A\l>   [NFECTIONS  OF  RESPIRATI  »i;v  TRACT 

middle  lobes  were  consolidated.  The  pleural  surface  of  the 
consolidated  areas  was  dull  m]  and  covered  by  a  small 
amount  of  fibrin.    The  lower  lobe,  with  the  exception  of  a 

small  part  at  the  summit,  was  very  firmly  consolidated,  on 
section  pinkish  gray  in  the  anterior  part  and  deep  rod  in  a 
small  /.one  at  the  posterior  border.  The  cu1  section  was 
conspicuously  granular.  The  trachea  and  bronchi  con- 
tained mucus.  Cultures  Prom  the  trachea,  the  right  lung 
and  the  right  pleural  cavity  contained  Pneumococcus  IV  in 
pure  culture.  Alveoli  in  the  consolidated  pari  of  the  lung 
were  filled  with  polynuclear  leucocytes  and  fibrin. 

Lobar  pneumonia  has  been  produced  by  the  introduction 
of  Pneumococcus  IV  into  the  trachea.  It  is  doubtful  if  pre- 
ceding inoculation  of  B.  influenza?  has  influenced  the  course 
of  the  disease. 

The  foregoing  experiments  have  shown  that  B.  influenzae 
introduced  into  the  nasopharynx  or  into  the  trachea  of 
monkeys  is  capable  of  causing  lesions  of  the  mucosa  of 
these  structures;  the  microorganism  persists  within  the 
nasopharynx  or  trachea  and  is  recoverable  during  a  vari- 
able period  of  from  two  to  eleven  days  after  inoculation. 
Spontaneous  infection  of  monkeys  with  B.  influenzae  has 
not  been  observed.  The  animals  infected  with  the  microor- 
ganism are  ill  during  several  days,  but  the  experimental 
disease  like  most  instances  of  human  influenza  is  self  lim- 
ited. Following  inoculation  of  the  nose  and  throat  of  mon- 
keys with  B.  influenzae  there  is  discharge  from  the  nose, 
tendency  to  epistaxis  and  absence  of  leucocytosis. 

Bronchitis  was  produced  by  the  introduction  of  B.  influ- 
enza' into  the  trachea  of  monkeys,  and  the  microorganism 
was  recovered  from  the  nasopharynx  two  and  three  days 
following  inoculation.  There  was  no  leucocytosis.  In  two 
experiments  death  occurred  following  inoculation,  and  in 
both  instances  it  was  found  that  the  animal  suffered  with 
tuberculosis  which  had  produced  only  trivial  lesions  of  the 


APPENDIX  397 

lungs.  In  both  animals  staphylococci  were  obtained  from 
the  internal  organs.  There  was  bronchitis  with  changes  in 
the  bronchi  which,  although  not  characteristic,  resembled 
those  found  in  association  with  B.  influenzae  in  man.  It  is 
noteworthy  that  B.  influenzae  is  usually  found  mixed  with 
other  bacteria  in  the  bronchi  of  those  who  have  died  with 
bronchitis  and  pneumonia  following  influenza.  In  the  ex- 
perimental animals  there  was  in  places  superficial  loss  of 
ciliated  epithelium,  exudation  of  polynuclear  leucocytes,  in- 
filtration of  the  subepithelial  tissue  with  plasma  cells  and 
hemorrhage  into  this  tissue. 

In  one  instance  simultaneous  injection  of  B.  influenzae  and 
S.  hemolyticus,  freshly  obtained  from  autopsy  upon  a  man 
dying  with  pneumonia  following  influenza,  caused  bronchi- 
tis and  bronchopneumonia;  there  were  acute  lymphangitis 
and  infiltration  of  the  interstitial  tissue  of  the  lung  with 
polynuclear  leucocytes  such  as  occurs  in  human  cases,  but 
the  lesion  had  not  proceeded  to  suppuration. 

In  man  B.  influenzae  is  usually  found  in  greatest  abun- 
dance upon  the  mucosa  of  the  respiratory  passages,  less 
frequently  it  invades  the  alveoli  of  the  lungs  and  is  almost 
invariably  found  in  association  with  other  microorganisms. 
In  company  with  other  microorganisms  B.  influenzae  pene- 
trates into  tissues  outside  the  lungs.  In  Experiment  7  it 
has  entered  the  pericardium,  with  streptococcus,  and  in 
Experiment  9  with  pneumococcus.  When  B.  influenzae  and 
streptococcus  are  injected  into  the  peritoneal  cavity  of  a 
mouse  both  organisms  appear  in  the  blood,  whereas  in  the 
absence  of  streptococcus,  B.  influenzae  seldom  leaves  the 
peritoneal  cavity. 

Typical  lobar  pneumonia  has  been  produced  for  the  first 
time  in  monkeys  by  injecting  pneumococci  (in  quantity  as 
small  as  0.33  c.c.  of  suspension)  into  the  trachea.  "With  the 
animals  available  it  has  not  been  possible  to  adjust  the  dos- 
age of  the  two  microorganisms  so  that  the  influence  of  one 


398      PNEUMONIAS  AND  INFECTIONS  OF  RESPIRATORY  TRACT 

upon  the  other  might  be  determined.  Pnenmoeoccus  III,  in 
small  quantity,  introduced  into  the  trachea  has  produced 
typical  acute  lobar  pneumonia  in  the  stage  of  gray  hepati- 
zation. A  similar  lesion  has  been  produced  with  Pneumo- 
coccus  IV  obtained  from  the  lung-  of  a  man  dead  with  pneu- 
monia. 


INDEX 


A 

Abscess  of  lung,  bacteriology  of,  203 
empyema  with,  233 
healing  of,  208 
measles  with,  347 
parotitis  with,  356 
pathogenesis   of,   205,   375 
scarlet  fever  with,  357 
staphylococcus  causing,  199,  225, 

366,    377 
S.  hemolyticus  causing,  199,   365 
Autopsies,  table  of,  118,  120,  335 
Autopsy     protocols,     No.     280,     226; 

No.    286,    226;     No.    312, 

254;     No.    322,    228;     No. 

330,    214;    No.    333,    229; 

No.    370,    229;     No.    376, 

206;    No.    379,    215;    No. 

380,    204;    No.    387,    206; 

No.    397,    223;     No.    406, 

204;    No.    416,    204;    No. 

420,    279;    No.    425,    229; 

No.    428,     280;     No.    433, 

280;     No.    445,    257;     No. 

465,    238;    No.    467,    208; 

No.     473,     236;    No.     474, 

221;     No.    487,    273;     No. 

499,     224;     No.    504,     238 


Bacillus  influenzae.  369 

bronchi  and, ' 178,   215,   346 
bronchitis   and,    153,    371 
experimental      inoculation      Avith, 

389 
history  of,   25 
influenza  and,  30,  42,  43,  46,  49, 

76,  370 
isolation  of,  30,  32,  38,  44. 
measles  with,  26,  40,  43,  295,  351 
meningitis  and,  26 
normal  men  carrying,  34,  42,  45, 

369 
pathogenicity    of,     26,    48,     370, 

387,  396 
pneumococcus     pneumonia     with, 

62,  178 


Bacillus  influenza — Cont'd 

pneumonia  with,  72,  75,  76,  173, 
364,    371 
Bronchi,      inflammation      of     mucous 

glands  of,  146 
Bronchiectasis,  239,  269,  355,  367 
abscess  with,  254 
bacteriology  of,  244 
bronchitis  Avith,  245 
measles  with,   336 
pathogenesis   of,   245,   259 
Bronchiolitis,   organizing,   264 
Bronchitis,   40,   142,   195,    359 

bacteriology  of,  56,   150,   164,   359, 

371 
bronchiectasis    with,    245 
chronic,   262 
clinical  course  of,  58 
measles  with,  336 
organizing,  264 

purulent,    47,    56,    60,    63,    74,    143, 
149,  153,  360 
Bronchopneumonia,    60,    63,    66,    162, 
360,  363 
bacteriology  of,   68,   163,   171,   176, 
181,    184,    189,    194,    197, 
345,  364 
fibrin  with,  182 

lobar  pneumonia  with,  155,  157 
measles  with,  340 

secondary  infection  by  S.  hemolyti- 
cus  with,  172,  177,  181, 
374 

C 

Carriers  of  B.  Influenza?,  46,  101,  369 

of  S.  hemolyticus.  99,  285,  287,  298, 

303,    309,    310,    315,    319, 

321,  332,  379 

Cartilage,  atrophy  with  bronchiectasis 

of,  254 
Contact    infection    in    influenza,    pre- 
vention of,  98 
in  measles,  289 

in  pneumonia,  prevention  of,  98 
Cubicles  to  prevent  contact  infection, 

98,  290 
Cyanosis,  144 


399 


401) 


INI'  E  \ 


E 

Empyema,  64,  67,  224,  226,  233,  304, 
366 

abscess  of  lung  and,  233 

encapsulated,  235 

interstitial    suppurative    pneumonia 
with,    216,   234 

measles  with,  ."•  is' 

pneumococcus,   236,   350 

streptococcus,  233,  350 
Endophlebitis,  219 

H 

Hemorrhagic  and  edematous  consolida- 
tion     with      bronchopneu- 
monia, 188 
peribronchiolar    consolidation    with 
b  r  o  n  c  hopncumonia,   163, 
17::,    272,   340 
Hepatization  with  bronchopneumonia, 
17!',  181 
with  lobar  pneumonia,  160 


Influenza,  B.  influenzae  with,  30,  73 
bronchitis  with,  55,  56 
clinical  course  of,  28,  53,  73,  80 
coryza  with,  5  I 
cyanosis  with,  54 
epidemic    in    fall   of  1918,  52,  108, 

359 
epidemic  in  spring  of  1918,  47 
fever  with,  53 

gastrointestinal  symptoms  with,  55 
laryngitis  with,  54 
lobar  pneumonia  and,  161 
measles    and,    292,    319,    331,    351, 

357,  380 
pandemic  of  1889-90,  109,  115 
pandemic  of  1918-1  it,  27,  359 
pharyngitis  with,  54 
pneumococcus  with,  33 
pneumonia  with,  55,  59,  74,  81,  139 
pulmonary  lesions  of,   137 
pulse  with,  54 
secondary  infection  with,  28,  15,  57, 

95 
sputum  with,  55 
S.   hemolyticus  with,   103 
Interstitial     bronchopneumonia,     261, 

278,  348 
suppurative    pneumonia,    199,    209, 

366,  376 
bacteriology  of,  214 


[nterstitial    suppurative    pneumonia — 
Cont'd 
chronic  inflammation  with,  221 
empyema   with,   216,   234 
healing  of,   222,  224 
measles   with,   348 
pericarditis    with,    2::7 


Lobar   pneumonia,   60,   63,    154,   360, 
362 

bacteriology  of,  64,  L56;  L64,  339, 
362 

bronchopneumonia  with,  155,  157 

experimental  production  in  mon- 
keys of,  394,  397 

influenza  and,  161 

measles  with,  337 

purulent  bronchitis  with,  60,  63, 
66 

secondary  infection  by  hemolytic 
streptococci  with,  64,  159, 
340,   374 

spread  in  lung  of,  339,  354 

typhoid   fever  with,   353 
Lobular  consolidation,  confluent,  188, 
341 

with  bronchopneumonia,  163,  178, 
272,  341 
Lymphatics,  suppurative  inflammation 
of,  217,   218,  376 
thrombosis  of,  217,  218 
Lymphangitis,    experimental    produc- 
tion    with     S.    hemolyticus 
of,  392 

M 

Masks   to    prevent    contact    infection, 

98,   290 
Mastoiditis,   303,   312,  332 
Measles,   119,  288 
B.  influenza?  with,  26,   in,  4::,  295 
bronchiectasis   with,   336 
bronchitis  with,  336 
bronchopneumonia   with,  340 
complications  of,  303,  378 
empyema  with,  349 
influenza    and,    292,   319,   331,   351, 

357,  380 
interstitial    suppurative    pneumonia 

with,  348 
lobar  pneumonia   with,   337 
pneumococcus  pneumonia   with,  312 
pneumonia  and,  292,  303,  312,  332, 

334,  378 
secondary  infection  w  ith,  282 


INIMiX 


401. 


Measles — font  'd 

S.  hemolyticus  with,  285,  287,  297, 

319,   330,   331,   353,   378 
suppurative    pneumonia    with,    345, 

347 
unresolved  bronchopneumonia  with, 
342 
Methods,  29,  51,  283,  291 
Mortality      of      pneumococcus     pneu- 
monia, 140 
of    pneumonia    following    influenza, 

139 
of  streptococcus  pneumonia,   140 
Mumps,  119,  355 


N 

Necrosis       with        bronchopneumonia 
caused   by   S.   liemolyticus, 
186,  375 
with  lobar  pneumonia  caused  by  S. 

liemolyticus,  160,  374 
with  S.  liemolyticus,  199,  200 

O 

Oedema,  interstitial,  209 
Organization    of    pneumonic    exudate, 

197 
Otitis  media,  289,  303,  312,  317,  329, 

332 


Peribronchiolar      consolidation      -with 
b  rone  hopneumonia,   163, 
166,  267,  340 
Pericarditis,  64,  237 
Peribronchial        consolidation        with 
b  r  o  n  c  hopneumonia,   163, 
192,  361 
hemorrhage,  189 
Peritonitis,  238 
Phagocytosis  of  red  blood  corpuscles, 

272 
Pneumococcus,  372 
bronchitis  and,   153 
bronchopneumonia    with,    165,    184, 

373 
empyema,  236 
experimental  lobar  pneumonia  with, 

393 
influenza  with,  33 
lobar  pneumonia  with,  158,  372 
pneumonia,  60,  75,  104 
clinical  course  of,  62 
measles  and,  312,  332 


I'neumococcus,    pneumonia — Cont'd 
mortality  of,  140 
secondary  pneumococcus  infection 

with,  61 
secondary  streptococcus   infection 

with,  62 
transmission  of,  91,  383 
secondary    infection    in    pneumonia 

with,  91 
Pneumonia,  B.   influenzae  causing,  72, 

76,   371 
bacteriology    of   influenza    and,    60, 

74,   107 
bacteriology  of  measles  and,  351 
chronic  fibroid,  273 
clinical  course  of  influenza  with,  62 
diagnosis  of,   136,  334,  361 
dissecans,  209 
immunity  following,  373 
influenza  with,  59,  76,  81,  109,  360 
measles    and,    119,    292,    303,    312, 

332,  334,  378 
mumps  and,  119 
pneumococcus,     see     Pneumococcus 

pneumonia 
prevention   of,  98,   319,   383 
scarlet  fever  and,  119 
secondary    infection    with,    83,    106 
spread  through  lungs  of,  194,  373 
staphylococcus,    see    Staphylococcus 

pneumonia 
streptococcus,       see      Streptococcus 

pneumonia 
S.  hemolyticus  in  throat  with,  310, 

329,  379 
Pseudoinfluenza   bacilli,    26 


S 

Scarlet  fever,  119,  356 
Squamous     transformation     of    bron- 
chial epithelium,  149,  251, 
275,  336 
Staphylococcus,   153,   377 

pneumonia,    112,    225,    354,   366 
pneumonia,  pathogenesis  of,  230 
Streptococcus    empyema,    233 
hemolyticus,  374 

bronchitis   with,    153 
dissemination  in  wards  of.  315 
experimental  production  of  acute 

lymphangitis  with,   392 
identification  of,  283 
influenza  with,  103 
lobar  pneumonia  with,  64,  159 
measles  with,  285,  287,  297,  330, 
331,    345,    353,   378 


40L1 


INIM'A 


Streptococcus  li  'molyticua — Cont  M 
normal  men  with,  285,  322 
secondary  infection  in  pneumonia 
with,  84,  L06,  L78,  204,  374 

nonhemolytic,  376 

peritonitis,  238 

pneumonia,  60,  70,  75,  11."),  307,  365 
bacteriology  of,  71 
clinical    features  of,   71 
measles  with,  303,  305,  307,  318 
mortality  of,   140 
transmission  of,  84,  381 

viridans,  377 
Suppurative  pneumonia,   li'!'.  ■"•17 
w ith  measles,  3 15,  347 


Thrombosis  of  capillaries  with  bron- 

chopneumonia,  184 
Typhoid  Eever,  lobar  pneumonia  with, 
353 
staphylococcus    pneumonia    with, 
'  354 


U 

Unresolved     bronchopneumonia,     261, 

I'tHi.  .".42,  3I5S 

bacteriology   of,  27(5 

interstitial      suppurative      pneu- 
monia  with,  278 


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This  book  is  due  on  the  date  indicated  below,  or  at  the 
expiration  of  a  definite  period  after  the  date  of  borrowing,  as 
provided  by  the  library  rules  or  by  special  arrangement  with 
the  Librarian  in  charge. 

DATE  BORROWED 

DATE   DUE 

DATE  BORROWED 

DATE  DUE 

N0V] 

fY*F 

C28( 3- 52) lOOM 

0p3 
1921 

Opie^  E.L. 

Epidemic  respiratoiy  disease. 


COLUMBIA  UNIVERSITY  LIBRARIES 


0041076354 


